Action potential

Action potential

Overview
In physiology
Physiology
Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...

, an action potential is a short-lasting event in which the electrical membrane potential
Membrane potential
Membrane potential is the difference in electrical potential between the interior and exterior of a biological cell. All animal cells are surrounded by a plasma membrane composed of a lipid bilayer with a variety of types of proteins embedded in it...

 of a cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

 rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells
Membrane potential
Membrane potential is the difference in electrical potential between the interior and exterior of a biological cell. All animal cells are surrounded by a plasma membrane composed of a lipid bilayer with a variety of types of proteins embedded in it...

, which include neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

s, muscle cells
Myocyte
A myocyte is the type of cell found in muscles. They arise from myoblasts.Each myocyte contains myofibrils, which are long, long chains of sarcomeres, the contractile units of the cell....

, and endocrine cells, as well as in some plant cell
Plant cell
Plant cells are eukaryotic cells that differ in several key respects from the cells of other eukaryotic organisms. Their distinctive features include:...

s. In neurons, they play a central role in cell-to-cell communication. In other types of cells, their main function is to activate intracellular processes.
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In physiology
Physiology
Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...

, an action potential is a short-lasting event in which the electrical membrane potential
Membrane potential
Membrane potential is the difference in electrical potential between the interior and exterior of a biological cell. All animal cells are surrounded by a plasma membrane composed of a lipid bilayer with a variety of types of proteins embedded in it...

 of a cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

 rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells
Membrane potential
Membrane potential is the difference in electrical potential between the interior and exterior of a biological cell. All animal cells are surrounded by a plasma membrane composed of a lipid bilayer with a variety of types of proteins embedded in it...

, which include neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

s, muscle cells
Myocyte
A myocyte is the type of cell found in muscles. They arise from myoblasts.Each myocyte contains myofibrils, which are long, long chains of sarcomeres, the contractile units of the cell....

, and endocrine cells, as well as in some plant cell
Plant cell
Plant cells are eukaryotic cells that differ in several key respects from the cells of other eukaryotic organisms. Their distinctive features include:...

s. In neurons, they play a central role in cell-to-cell communication. In other types of cells, their main function is to activate intracellular processes. In muscle cells, for example, an action potential is the first step in the chain of events leading to contraction. In beta cell
Beta cell
Beta cells are a type of cell in the pancreas located in the so-called islets of Langerhans. They make up 65-80% of the cells in the islets.-Function:...

s of the pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...

, they provoke release of insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....

. Action potentials in neurons are also known as "nerve impulses" or "spikes", and the temporal sequence of action potentials generated by a neuron is called its "spike train". A neuron that emits an action potential is often said to "fire".

Action potentials are generated by special types of voltage-gated ion channel
Voltage-gated ion channel
Voltage-gated ion channels are a class of transmembrane ion channels that are activated by changes in electrical potential difference near the channel; these types of ion channels are especially critical in neurons, but are common in many types of cells....

s embedded in a cell's plasma membrane. These channels are shut when the membrane potential is near the resting potential
Resting potential
The relatively static membrane potential of quiescent cells is called the resting membrane potential , as opposed to the specific dynamic electrochemical phenomena called action potential and graded membrane potential....

 of the cell, but they rapidly begin to open if the membrane potential increases to a precisely defined threshold value. When the channels open, they allow an inward flow of sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...

 ions, which changes the electrochemical gradient, which in turn produces a further rise in the membrane potential. This then causes more channels to open, producing a greater electric current, and so on. The process proceeds explosively until all of the available ion channels are open, resulting in a large upswing in the membrane potential. The rapid influx of sodium ions causes the polarity of the plasma membrane to reverse, and the ion channels then rapidly inactivate. As the sodium channels close, sodium ions can no longer enter the neuron, and they are actively transported out of the plasma membrane. Potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...

 channels are then activated, and there is an outward current of potassium ions, returning the electrochemical gradient to the resting state. After an action potential has occurred, there is a transient negative shift, called the afterhyperpolarization
Afterhyperpolarization
Afterhyperpolarization or AHP describes the hyperpolarization phase of a neuron's action potential where the cell's membrane potential falls below the normal resting potential. This is also commonly referred to as an action potential's undershoot phase...

 or refractory period, due to additional potassium currents. This is the mechanism which prevents an action potential traveling back the way it just came.

In animal cells, there are two primary types of action potentials, one type generated by voltage-gated sodium channels, the other by voltage-gated calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

 channels. Sodium-based action potentials usually last for less than one millisecond, whereas calcium-based action potentials may last for 100 milliseconds or longer. In some types of neurons, slow calcium spikes provide the driving force for a long burst of rapidly-emitted sodium spikes. In cardiac muscle cells, on the other hand, an initial fast sodium spike provides a "primer" to provoke the rapid onset of a calcium spike, which then produces muscle contraction.

Function


Nearly all cells from animals, plants and fungi function as batteries, in the sense that they maintain a voltage difference between the interior and the exterior of the cell, with the interior being the negative pole of the battery. The voltage of a cell is usually measured in millivolts (mV), or thousandths of a volt. A typical voltage for an animal cell is –70 mV—approximately one-fifteenth of a volt. Because cells are so small, voltages of this magnitude give rise to very strong electric forces within the cell membrane.

In the majority of cells, the voltage
Membrane potential
Membrane potential is the difference in electrical potential between the interior and exterior of a biological cell. All animal cells are surrounded by a plasma membrane composed of a lipid bilayer with a variety of types of proteins embedded in it...

 changes very little over time. There are some types of cells, however, that are electrically active in the sense that their voltages fluctuate. In some of these, the voltages sometimes show very rapid up-and-down fluctuations that have a stereotyped form: These up-and-down cycles are known as action potentials. The durations of action potentials vary across a wide range. In brain cells of animals, the entire up-and-down cycle may take place in less than a thousandth of a second. In other types of cells, the cycle may last for several seconds.

The electrical properties of an animal cell are determined by the structure of the membrane that surrounds it. A cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

 consists of a layer of lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...

 molecules with larger protein molecules embedded in it. The lipid layer is highly resistant to movement of electrically charged ions, so it functions mainly as an insulator. The large membrane-embedded molecules, in contrast, provide channels through which ions can pass across the membrane, and some of the large molecules are capable of actively moving specific types of ions from one side of the membrane to the other.

Process in a typical neuron



All cells in animal body tissues are electrically polarized — in other words, they maintain a voltage difference across the cell's plasma membrane, known as the membrane potential
Membrane potential
Membrane potential is the difference in electrical potential between the interior and exterior of a biological cell. All animal cells are surrounded by a plasma membrane composed of a lipid bilayer with a variety of types of proteins embedded in it...

. This electrical polarization results from a complex interplay between protein structures embedded in the membrane called ion pumps and ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...

s. In neurons, the types of ion channels in the membrane usually vary across different parts of the cell, giving the dendrite
Dendrite
Dendrites are the branched projections of a neuron that act to conduct the electrochemical stimulation received from other neural cells to the cell body, or soma, of the neuron from which the dendrites project...

s, axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....

, and cell body
Soma (biology)
The soma , or perikaryon , or cyton, is the bulbous end of a neuron, containing the cell nucleus. The word "soma" comes from the Greek σῶμα, meaning "body"; the soma of a neuron is often called the "cell body"...

 different electrical properties. As a result, some parts of the membrane of a neuron may be excitable (capable of generating action potentials), whereas others are not. The most excitable part of a neuron is usually the axon hillock
Axon hillock
The axon hillock is a specialized part of the cell body of a neuron that connects to the axon. As a result, the axon hillock is the last site in the soma where membrane potentials propagated from synaptic inputs are summated before being transmitted to the axon. For many years it was believed...

 (the point where the axon leaves the cell body), but the axon and cell body are also excitable in most cases.

Each excitable patch of membrane has two important levels of membrane potential: the resting potential
Resting potential
The relatively static membrane potential of quiescent cells is called the resting membrane potential , as opposed to the specific dynamic electrochemical phenomena called action potential and graded membrane potential....

, which is the value the membrane potential maintains as long as nothing perturbs the cell, and a higher value called the threshold potential
Threshold potential
The threshold potential is the membrane potential to which a membrane must be depolarized to initiate an action potential.It often can be between −40 and -55 mV, but it can vary based upon several factors...

. At the axon hillock of a typical neuron, the resting potential is around -70 millivolts (mV) and the threshold potential is around -55 mV. Synaptic inputs to a neuron cause the membrane to depolarize
Depolarization
In biology, depolarization is a change in a cell's membrane potential, making it more positive, or less negative. In neurons and some other cells, a large enough depolarization may result in an action potential...

 or hyperpolarize
Hyperpolarization (biology)
Hyperpolarization is a change in a cell's membrane potential that makes it more negative. It is the opposite of a depolarization.Hyperpolarization is often caused by efflux of K+ through K+ channels, or influx of Cl– through Cl– channels. On the other hand, influx of cations, e.g...

; that is, they cause the membrane potential to rise or fall. Action potentials are triggered when enough depolarization accumulates to bring the membrane potential up to threshold. When an action potential is triggered, the membrane potential abruptly shoots upward, often reaching as high as +100 mV, then equally abruptly shoots back downward, often ending below the resting level, where it remains for some period of time. The shape of the action potential is stereotyped; that is, the rise and fall usually have approximately the same amplitude and time course for all action potentials in a given cell. (Exceptions are discussed later in the article.) In most neurons, the entire process takes place in less than a thousandth of a second. Many types of neurons emit action potentials constantly at rates of up to 10-100 per second; some types, however, are much quieter, and may go for minutes or longer without emitting any action potentials.

Biophysical basis


Action potentials result from the presence in a cell's membrane of special types of voltage-gated ion channel
Voltage-gated ion channel
Voltage-gated ion channels are a class of transmembrane ion channels that are activated by changes in electrical potential difference near the channel; these types of ion channels are especially critical in neurons, but are common in many types of cells....

s. A voltage-gated ion channel is a cluster of proteins embedded in the membrane that has three key properties:
  1. It is capable of assuming more than one conformation.
  2. At least one of the conformations creates a channel through the membrane that is permeable to specific types of ions.
  3. The transition between conformations is influenced by the membrane potential.


Thus, a voltage-gated ion channel tends to be open for some values of the membrane potential, and closed for others. In most cases, however, the relationship between membrane potential and channel state is probabilistic and involves a time delay. Ions channels switch between conformations at unpredictable times: The membrane potential determines the rate of transitions and the probability per unit time of each type of transition.

Voltage-gated ion channels are capable of producing action potentials because they can give rise to positive feedback
Positive feedback
Positive feedback is a process in which the effects of a small disturbance on a system include an increase in the magnitude of the perturbation. That is, A produces more of B which in turn produces more of A. In contrast, a system that responds to a perturbation in a way that reduces its effect is...

 loops: The membrane potential controls the state of the ion channels, but the state of the ion channels controls the membrane potential. Thus, in some situations, a rise in the membrane potential can cause ion channels to open, thereby causing a further rise in the membrane potential. An action potential occurs when this positive feedback cycle proceeds explosively. The time and amplitude trajectory of the action potential are determined by the biophysical properties of the voltage-gated ion channels that produce it. Several types of channels that are capable of producing the positive feedback necessary to generate an action potential exist. Voltage-gated sodium channels are responsible for the fast action potentials involved in nerve conduction. Slower action potentials in muscle cells and some types of neurons are generated by voltage-gated calcium channels. Each of these types comes in multiple variants, with different voltage sensitivity and different temporal dynamics.

The most intensively studied type of voltage-dependent ion channels comprises the sodium channels involved in fast nerve conduction. These are sometimes known as Hodgkin-Huxley sodium channels because they were first characterized by Alan Hodgkin
Alan Lloyd Hodgkin
Sir Alan Lloyd Hodgkin, OM, KBE, PRS was a British physiologist and biophysicist, who shared the 1963 Nobel Prize in Physiology or Medicine with Andrew Huxley and John Eccles....

 and Andrew Huxley
Andrew Huxley
Sir Andrew Fielding Huxley, OM, FRS is an English physiologist and biophysicist, who won the 1963 Nobel Prize in Physiology or Medicine for his experimental and mathematical work with Sir Alan Lloyd Hodgkin on the basis of nerve action potentials, the electrical impulses that enable the activity...

 in their Nobel Prize-winning studies of the biophysics of the action potential, but can more conveniently be referred to as NaV channels. (The "V" stands for "voltage".) An NaV channel has three possible states, known as deactivated, activated, and inactivated. The channel is permeable only to sodium ions when it is in the activated state. When the membrane potential is low, the channel spends most of its time in the deactivated (closed) state. If the membrane potential is raised above a certain level, the channel shows increased probability of transitioning to the activated (open) state. The higher the membrane potential the greater the probability of activation. Once a channel has activated, it will eventually transition to the inactivated (closed) state. It tends then to stay inactivated for some time, but, if the membrane potential becomes low again, the channel will eventually transition back to the deactivated state. During an action potential, most channels of this type go through a cycle deactivated→activated→inactivated→deactivated. This is only the population average behavior, however — an individual channel can in principle make any transition at any time. However, the likelihood of a channel's transitioning from the inactivated state directly to the activated state is very low: A channel in the inactivated state is refractory until it has transitioned back to the deactivated state.

The outcome of all this is that the kinetics of the NaV channels are governed by a transition matrix whose rates are voltage-dependent in a complicated way. Since these channels themselves play a major role in determining the voltage, the global dynamics of the system can be quite difficult to work out. Hodgkin and Huxley approached the problem by developing a set of differential equation
Differential equation
A differential equation is a mathematical equation for an unknown function of one or several variables that relates the values of the function itself and its derivatives of various orders...

s for the parameters that govern the ion channel states, known as the Hodgkin-Huxley equations. These equations have been extensively modified by later research, but form the starting point for most theoretical studies of action potential biophysics.
As the membrane potential is increased, sodium ion channels open, allowing the entry of sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...

 ions into the cell. This is followed by the opening of potassium ion channels
Potassium channel
In the field of cell biology, potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium-selective pores that span cell membranes...

 that permit the exit of potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...

 ions from the cell. The inward flow of sodium ions increases the concentration of positively-charged cations in the cell and causes depolarization, where the potential of the cell is higher than the cell's resting potential
Resting potential
The relatively static membrane potential of quiescent cells is called the resting membrane potential , as opposed to the specific dynamic electrochemical phenomena called action potential and graded membrane potential....

. The sodium channels close at the peak of the action potential, while potassium continues to leave the cell. The efflux of potassium ions decreases the membrane potential or hyperpolarizes the cell. For small voltage increases from rest, the potassium current exceeds the sodium current and the voltage returns to its normal resting value, typically −70 mV. However, if the voltage increases past a critical threshold, typically 15 mV higher than the resting value, the sodium current dominates. This results in a runaway condition whereby the positive feedback
Positive feedback
Positive feedback is a process in which the effects of a small disturbance on a system include an increase in the magnitude of the perturbation. That is, A produces more of B which in turn produces more of A. In contrast, a system that responds to a perturbation in a way that reduces its effect is...

 from the sodium current activates even more sodium channels. Thus, the cell "fires," producing an action potential.

Currents produced by the opening of voltage-gated channels in the course of an action potential are typically significantly larger than the initial stimulating current. Thus, the amplitude, duration, and shape of the action potential are determined largely by the properties of the excitable membrane and not the amplitude or duration of the stimulus. This all-or-nothing
All-or-none law
The all-or-none law is the principle that the strength by which a nerve or muscle fiber responds to a stimulus is not dependent on the strength of the stimulus...

 property of the action potential sets it apart from graded potentials such as receptor potential
Receptor potential
Receptor potential, a type of graded potential, is the transmembrane potential difference of a sensory receptor.A receptor potential is often produced by sensory transduction. It is generally a depolarizing event resulting from inward current flow...

s, electrotonic potential
Electrotonic potential
In physiology, electrotonus refers to the "passive" spread of charge inside a neuron. "Passive" means that voltage-dependent changes in membrane conductance do not contribute. Neurons and other excitable cells produce two types of electrical potential. The first is a non-propagated local potential...

s, and synaptic potential
Synaptic potential
A synaptic potential is an alteration in the membrane potential of a cell resulting from activation of a synaptic input...

s, which scale with the magnitude of the stimulus. A variety of action potential types exist in many cell types and cell compartments as determined by the types of voltage-gated channels, leak channels, channel distributions, ionic concentrations, membrane capacitance, temperature, and other factors.

The principal ions involved in an action potential are sodium and potassium cations; sodium ions enter the cell, and potassium ions leave, restoring equilibrium. Relatively few ions need to cross the membrane for the membrane voltage to change drastically. The ions exchanged during an action potential, therefore, make a negligible change in the interior and exterior ionic concentrations. The few ions that do cross are pumped out again by the continuous action of the sodium–potassium pump, which, with other ion transporters, maintains the normal ratio of ion concentrations across the membrane. Calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

 cations and chloride
Chloride
The chloride ion is formed when the element chlorine, a halogen, picks up one electron to form an anion Cl−. The salts of hydrochloric acid HCl contain chloride ions and can also be called chlorides. The chloride ion, and its salts such as sodium chloride, are very soluble in water...

 anions are involved in a few types of action potentials, such as the cardiac action potential
Cardiac action potential
In electrocardiography, the cardiac action potential is a specialized action potential in the heart, necessary for the electrical conduction system of the heart....

 and the action potential in the single-cell alga
Algae
Algae are a large and diverse group of simple, typically autotrophic organisms, ranging from unicellular to multicellular forms, such as the giant kelps that grow to 65 meters in length. They are photosynthetic like plants, and "simple" because their tissues are not organized into the many...

 Acetabularia
Acetabularia
Acetabularia is a genus of green algae, specifically of the Polyphysaceae family, Typically found in subtropical waters, Acetabularia is a single-celled organism, but gigantic in size and complex in form, making it an excellent model organism for studying cell biology...

, respectively.

Although action potentials are generated locally on patches of excitable membrane, the resulting currents can trigger action potentials on neighboring stretches of membrane, precipitating a domino-like propagation. In contrast to passive spread of electric potentials (electrotonic potential
Electrotonic potential
In physiology, electrotonus refers to the "passive" spread of charge inside a neuron. "Passive" means that voltage-dependent changes in membrane conductance do not contribute. Neurons and other excitable cells produce two types of electrical potential. The first is a non-propagated local potential...

), action potentials are generated anew along excitable stretches of membrane and propagate without decay. Myelinated sections of axons are not excitable and do not produce action potentials and the signal is propagated passively as electrotonic potential
Electrotonic potential
In physiology, electrotonus refers to the "passive" spread of charge inside a neuron. "Passive" means that voltage-dependent changes in membrane conductance do not contribute. Neurons and other excitable cells produce two types of electrical potential. The first is a non-propagated local potential...

. Regularly spaced unmyelinated patches, called the nodes of Ranvier
Nodes of Ranvier
Myelin sheath gaps or nodes of Ranvier are the gaps formed between the myelin sheaths generated by different cells. A myelin sheath is a many-layered coating, largely composed of a fatty substance called myelin, that wraps around the axon of a neuron and very efficiently insulates it...

, generate action potentials to boost the signal. Known as saltatory conduction
Saltatory conduction
Saltatory conduction is the propagation of action potentials along myelinated axons from one node of Ranvier to the next node, increasing the conduction velocity of action potentials without needing to increase the diameter of an axon.-Mechanism:Because the cytoplasm of the axon is electrically...

, this type of signal propagation provides a favorable tradeoff of signal velocity and axon diameter. Depolarization of axon terminal
Axon terminal
Axon terminals are distal terminations of the branches of an axon. An axon nerve fiber is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body, or soma, in order to transmit those impulses to other neurons.Neurons are...

s, in general, triggers the release of neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

 into the synaptic cleft. In addition, backpropagating action potentials have been recorded in the dendrites of pyramidal neurons
Pyramidal cell
Pyramidal neurons are a type of neuron found in areas of the brain including cerebral cortex, the hippocampus, and in the amygdala. Pyramidal neurons are the primary excitation units of the mammalian prefrontal cortex and the corticospinal tract. Pyramidal neurons were first discovered and...

, which are ubiquitous in the neocortex. These are thought to have a role in spike-timing-dependent plasticity.

Anatomy of a neuron



Several types of cells support an action potential, such as plant cells, muscle cells, and the specialized cells of the heart (in which occurs the cardiac action potential
Cardiac action potential
In electrocardiography, the cardiac action potential is a specialized action potential in the heart, necessary for the electrical conduction system of the heart....

). However, the main excitable cell is the neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

, which also has the simplest mechanism for the action potential.

Neurons are electrically excitable cells composed, in general, of one or more dendrite
Dendrite
Dendrites are the branched projections of a neuron that act to conduct the electrochemical stimulation received from other neural cells to the cell body, or soma, of the neuron from which the dendrites project...

s, a single soma, a single axon and one or more axon terminals. The dendrite is one of the two types of synapses
Chemical synapse
Chemical synapses are specialized junctions through which neurons signal to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous system. They are crucial to the biological computations that underlie...

, the other being the axon terminal boutons. Dendrites form protrusions in response to the axon terminal boutons. These protrusions, or spines, are designed to capture the neurotransmitters released by the presynaptic neuron. They have a high concentration of ligand activated channels. It is, therefore, here where synapses from two neurons communicate with one another. These spines have a thin neck connecting a bulbous protrusion to the main dendrite. This ensures that changes occurring inside the spine are less likely to affect the neighbouring spines. The dendritic spine can, therefore, with rare exception (see LTP), act as an independent unit. The dendrites then connect onto the soma
Soma (biology)
The soma , or perikaryon , or cyton, is the bulbous end of a neuron, containing the cell nucleus. The word "soma" comes from the Greek σῶμα, meaning "body"; the soma of a neuron is often called the "cell body"...

. The soma houses the nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...

, which acts as the regulator for the neuron. Unlike the spines, the surface of the soma is populated by voltage activated ion channels. These channels help transmit the signals generated by the dendrites. Emerging out from the soma is the axon hillock
Axon hillock
The axon hillock is a specialized part of the cell body of a neuron that connects to the axon. As a result, the axon hillock is the last site in the soma where membrane potentials propagated from synaptic inputs are summated before being transmitted to the axon. For many years it was believed...

. This region is characterized by having an incredibly high concentration of voltage-activated sodium channels. In general, it is considered to be the spike initiation zone for action potentials. Multiple signals generated at the spines, and transmitted by the soma all converge here. Immediately after the axon hillock is the axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....

. This is a thin tubular protrusion traveling away from the soma. The axon is insulated by a myelin
Myelin
Myelin is a dielectric material that forms a layer, the myelin sheath, usually around only the axon of a neuron. It is essential for the proper functioning of the nervous system. Myelin is an outgrowth of a type of glial cell. The production of the myelin sheath is called myelination...

 sheath. Myelin is composed of Schwann cells that wrap themselves multiple times around the axonal segment. This forms a thick fatty layer that prevents ions from entering or escaping the axon. This insulation prevents significant signal decay as well as ensuring faster signal speed. This insulation, however, has the restriction that no channels can be present on the surface of the axon. There are, therefore, regularly spaced patches of membrane, which have no insulation. These nodes of ranvier
Nodes of Ranvier
Myelin sheath gaps or nodes of Ranvier are the gaps formed between the myelin sheaths generated by different cells. A myelin sheath is a many-layered coating, largely composed of a fatty substance called myelin, that wraps around the axon of a neuron and very efficiently insulates it...

 can be considered to be 'mini axon hillocks', as their purpose is to boost the signal in order to prevent significant signal decay. At the furthest end, the axon loses its insulation and begins to branch into several axon terminals. These axon terminals then end in the form the second class of synapses, axon terminal buttons. These buttons have voltage-activated calcium channels, which come into play when signaling other neurons.

Initiation


Before considering the propagation of action potentials along axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....

s and their termination at the synaptic knobs, it is helpful to consider the methods by which action potentials can be initiated at the axon hillock
Axon hillock
The axon hillock is a specialized part of the cell body of a neuron that connects to the axon. As a result, the axon hillock is the last site in the soma where membrane potentials propagated from synaptic inputs are summated before being transmitted to the axon. For many years it was believed...

. The basic requirement is that the membrane voltage at the hillock be raised above the threshold for firing. There are several ways in which this depolarization can occur.


Dynamics


Action potentials are most commonly initiated by excitatory postsynaptic potential
Excitatory postsynaptic potential
In neuroscience, an excitatory postsynaptic potential is a temporary depolarization of postsynaptic membrane potential caused by the flow of positively charged ions into the postsynaptic cell as a result of opening of ligand-sensitive channels...

s from a presynaptic neuron. Typically, neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

 molecules are released by the presynaptic
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...

 neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

. These neurotransmitters then bind to receptors on the postsynaptic cell. This binding opens various types of ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...

s. This opening has the further effect of changing the local permeability of the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

 and, thus, the membrane potential. If the binding increases the voltage (depolarizes the membrane), the synapse is excitatory. If, however, the binding decreases the voltage (hyperpolarizes the membrane), it is inhibitory. Whether the voltage is decreased or increased, the change propagates passively to nearby regions of the membrane (as described by the cable equation and its refinements). Typically, the voltage stimulus decays exponentially with the distance from the synapse and with time from the binding of the neurotransmitter. Some fraction of an excitatory voltage may reach the axon hillock
Axon hillock
The axon hillock is a specialized part of the cell body of a neuron that connects to the axon. As a result, the axon hillock is the last site in the soma where membrane potentials propagated from synaptic inputs are summated before being transmitted to the axon. For many years it was believed...

 and may (in rare cases) depolarize the membrane enough to provoke a new action potential. More typically, the excitatory potentials from several synapses must work together at nearly the same time to provoke a new action potential. Their joint efforts can be thwarted, however, by the counteracting inhibitory postsynaptic potential
Inhibitory postsynaptic potential
An inhibitory postsynaptic potential is a synaptic potential that decreases the chance that a future action potential will occur in a postsynaptic neuron or α-motoneuron...

s.

Neurotransmission can also occur through electrical synapse
Electrical synapse
An electrical synapse is a mechanical and electrically conductive link between two abutting neurons that is formed at a narrow gap between the pre- and postsynaptic neurons known as a gap junction. At gap junctions, such cells approach within about 3.5 nm of each other, a much shorter...

s. Due to the direct connection between excitable cells in the form of gap junction
Gap junction
A gap junction or nexus is a specialized intercellular connection between a multitude of animal cell-types. It directly connects the cytoplasm of two cells, which allows various molecules and ions to pass freely between cells....

s, an action potential can be transmitted directly from one cell to the next in either direction. The free flow of ions between cells enables rapid non-chemical-mediated transmission. Rectifying channels ensure that action potentials move only in one direction through an electrical synapse. Electrical synapses are found in all nervous systems, including the human brain, although they are a distinct minority.

"All-or-none" principle


The amplitude
Amplitude
Amplitude is the magnitude of change in the oscillating variable with each oscillation within an oscillating system. For example, sound waves in air are oscillations in atmospheric pressure and their amplitudes are proportional to the change in pressure during one oscillation...

 of an action potential is independent of the amount of current that produced it. In other words, larger currents do not create larger action potentials. Therefore, action potentials are said to be all-or-none (or boolean
Boolean domain
In mathematics and abstract algebra, a Boolean domain is a set consisting of exactly two elements whose interpretations include false and true...

), since either they occur fully or they do not occur at all. Instead, the frequency
Frequency
Frequency is the number of occurrences of a repeating event per unit time. It is also referred to as temporal frequency.The period is the duration of one cycle in a repeating event, so the period is the reciprocal of the frequency...

 of action potentials is what encodes for the intensity of a stimulus. This is in contrast to receptor potential
Receptor potential
Receptor potential, a type of graded potential, is the transmembrane potential difference of a sensory receptor.A receptor potential is often produced by sensory transduction. It is generally a depolarizing event resulting from inward current flow...

s, whose amplitudes are dependent on the intensity of a stimulus.

Sensory neurons


In sensory neurons, an external signal such as pressure, temperature, light, or sound is coupled with the opening and closing of ion channels, which in turn alter the ionic permeabilities of the membrane and its voltage. These voltage changes can again be excitatory (depolarizing) or inhibitory (hyperpolarizing) and, in some sensory neurons, their combined effects can depolarize the axon hillock enough to provoke action potentials. Examples in humans include the olfactory receptor neuron
Olfactory receptor neuron
An olfactory receptor neuron , also called an olfactory sensory neuron , is a transduction cell within the olfactory system. J. Rospars, Dendritic integration in olfactory sensory neurons: a steady-state analysis of how the neuron structure and neuron environment influence the coding of odor...

 and Meissner's corpuscle
Meissner's corpuscle
Meissner's corpuscles are a type of mechanoreceptor. They are a type of nerve ending in the skin that is responsible for sensitivity to light touch. In particular, they have highest sensitivity when sensing vibrations lower than 50 Hertz...

, which are critical for the sense of smell
Olfaction
Olfaction is the sense of smell. This sense is mediated by specialized sensory cells of the nasal cavity of vertebrates, and, by analogy, sensory cells of the antennae of invertebrates...

 and touch
Somatosensory system
The somatosensory system is a diverse sensory system composed of the receptors and processing centres to produce the sensory modalities such as touch, temperature, proprioception , and nociception . The sensory receptors cover the skin and epithelia, skeletal muscles, bones and joints, internal...

, respectively. However, not all sensory neurons convert their external signals into action potentials; some do not even have an axon! Instead, they may convert the signal into the release of a neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

, or into continuous graded potentials
Receptor potential
Receptor potential, a type of graded potential, is the transmembrane potential difference of a sensory receptor.A receptor potential is often produced by sensory transduction. It is generally a depolarizing event resulting from inward current flow...

, either of which may stimulate subsequent neuron(s) into firing an action potential. For illustration, in the human ear
Ear
The ear is the organ that detects sound. It not only receives sound, but also aids in balance and body position. The ear is part of the auditory system....

, hair cell
Hair cell
Hair cells are the sensory receptors of both the auditory system and the vestibular system in all vertebrates. In mammals, the auditory hair cells are located within the organ of Corti on a thin basilar membrane in the cochlea of the inner ear...

s convert the incoming sound into the opening and closing of mechanically gated ion channels
Stretch-activated ion channel
Stretch-activated or stretch-gated ion channels are ion channels which open their pores in response to mechanical deformation of a neuron's plasma membrane. Stretch-activated channels were first observed in chick skeletal muscles by Falguni Guharay and Frederick Sachs in 1983 and the results were...

, which may cause neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

 molecules to be released. In similar manner, in the human retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...

, the initial photoreceptor cells and the next two layers of cells (bipolar cell
Bipolar cell
As a part of the retina, the bipolar cell exists between photoreceptors and ganglion cells. They act, directly or indirectly, to transmit signals from the photoreceptors to the ganglion cells.-Overview:...

s and horizontal cell
Horizontal cell
Horizontal cells are the laterally interconnecting neurons in the outer plexiform layer of the retina of mammalian eyes. They help integrate and regulate the input from multiple photoreceptor cells...

s) do not produce action potentials; only some amacrine cell
Amacrine cell
Amacrine cells are interneurons in the retina. Amacrine cells are responsible for 70% of input to retinal ganglion cells. Bipolar cells, which are responsible for the other 30% of input to retinal ganglia, are regulated by amacrine cells.-Overview:...

s and the third layer, the ganglion cell
Ganglion cell
A retinal ganglion cell is a type of neuron located near the inner surface of the retina of the eye. It receives visual information from photoreceptors via two intermediate neuron types: bipolar cells and amacrine cells...

s, produce action potentials, which then travel up the optic nerve
Optic nerve
The optic nerve, also called cranial nerve 2, transmits visual information from the retina to the brain. Derived from the embryonic retinal ganglion cell, a diverticulum located in the diencephalon, the optic nerve doesn't regenerate after transection.-Anatomy:The optic nerve is the second of...

.

Pacemaker potentials


In sensory neurons, action potentials result from an external stimulus. However, some excitable cells require no such stimulus to fire: They spontaneously depolarize their axon hillock and fire action potentials at a regular rate, like an internal clock. The voltage traces of such cells are known as pacemaker potential
Pacemaker potential
In the pacemaking cells of the heart , the pacemaker potential is the slow, positive increase in voltage across the cell's membrane that occurs between the end of one action potential and the beginning of the next action potential...

s. The cardiac pacemaker
Cardiac pacemaker
right|thumb|350px|Image showing the cardiac pacemaker which is the SA nodeThe contraction of heart muscle in all animals with hearts is initiated by chemical impulses. The rate at which these impulses fire controls the heart rate...

 cells of the sinoatrial node
Sinoatrial node
The sinoatrial node is the impulse-generating tissue located in the right atrium of the heart, and thus the generator of normal sinus rhythm. It is a group of cells positioned on the wall of the right atrium, near the entrance of the superior vena cava...

 in the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...

 provide a good example. Although such pacemaker potentials have a natural rhythm, it can be adjusted by external stimuli; for instance, heart rate
Heart rate
Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....

 can be altered by pharmaceuticals as well as signals from the sympathetic
Sympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...

 and parasympathetic
Parasympathetic nervous system
The parasympathetic nervous system is one of the two main divisions of the autonomic nervous system . The ANS is responsible for regulation of internal organs and glands, which occurs unconsciously...

 nerves. The external stimuli do not cause the cell's repetitive firing, but merely alter its timing. In some cases, the regulation of frequency can be more complex, leading to patterns of action potentials, such as bursting
Bursting
Bursting is an extremely diverse general phenomenon of the activation patterns of neurons in the central nervous system and spinal cord where periods of rapid spiking are followed by quiescent, silent, periods. Bursting is thought to be important in the operation of robust central pattern...

.

Phases


The course of the action potential can be divided into five parts: the rising phase, the peak phase, the falling phase, the undershoot phase, and the refractory period. During the rising phase the membrane potential depolarizes (becomes more positive). The point at which depolarization stops is called the peak phase. At this stage, the membrane potential reaches a maximum. Subsequent to this, there is a falling phase. During this stage the membrane potential hyperpolarizes (becomes more negative). The undershoot phase is the point during which the membrane potential becomes temporarily more negatively charged than when at rest. Finally, the time during which a subsequent action potential is impossible or difficult to fire is called the refractory period, which may overlap with the other phases.

The course of the action potential is determined by two coupled effects. First, voltage-sensitive ion channels open and close in response to changes in the membrane voltage
Membrane potential
Membrane potential is the difference in electrical potential between the interior and exterior of a biological cell. All animal cells are surrounded by a plasma membrane composed of a lipid bilayer with a variety of types of proteins embedded in it...

 Vm. This changes the membrane's permeability to those ions. Second, according to the Goldman equation
Goldman equation
The Goldman–Hodgkin–Katz voltage equation, more commonly known as the Goldman equation is used in cell membrane physiology to determine the equilibrium potential across a cell's membrane taking into account all of the ions that are permeant through that membrane.The discoverers of this are David E...

, this change in permeability changes in the equilibrium potential Em, and, thus, the membrane voltage Vm. Thus, the membrane potential affects the permeability, which then further affects the membrane potential. This sets up the possibility for positive feedback
Positive feedback
Positive feedback is a process in which the effects of a small disturbance on a system include an increase in the magnitude of the perturbation. That is, A produces more of B which in turn produces more of A. In contrast, a system that responds to a perturbation in a way that reduces its effect is...

, which is a key part of the rising phase of the action potential. A complicating factor is that a single ion channel may have multiple internal "gates" that respond to changes in Vm in opposite ways, or at different rates. For example, although raising Vm opens most gates in the voltage-sensitive sodium channel, it also closes the channel's "inactivation gate", albeit more slowly. Hence, when Vm is raised suddenly, the sodium channels open initially, but then close due to the slower inactivation.

The voltages and currents of the action potential in all of its phases were modeled accurately by Alan Lloyd Hodgkin
Alan Lloyd Hodgkin
Sir Alan Lloyd Hodgkin, OM, KBE, PRS was a British physiologist and biophysicist, who shared the 1963 Nobel Prize in Physiology or Medicine with Andrew Huxley and John Eccles....

 and Andrew Huxley
Andrew Huxley
Sir Andrew Fielding Huxley, OM, FRS is an English physiologist and biophysicist, who won the 1963 Nobel Prize in Physiology or Medicine for his experimental and mathematical work with Sir Alan Lloyd Hodgkin on the basis of nerve action potentials, the electrical impulses that enable the activity...

 in 1952, for which they were awarded the Nobel Prize in Physiology or Medicine
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...

 in 1963. However, their model considers only two types of voltage-sensitive ion channels, and makes several assumptions about them, e.g., that their internal gates open and close independently of one another. In reality, there are many types of ion channels, and they do not always open and close independently.

Stimulation and rising phase


A typical action potential begins at the axon hillock
Axon hillock
The axon hillock is a specialized part of the cell body of a neuron that connects to the axon. As a result, the axon hillock is the last site in the soma where membrane potentials propagated from synaptic inputs are summated before being transmitted to the axon. For many years it was believed...

 with a sufficiently strong depolarization, e.g., a stimulus that increases Vm. This depolarization is often caused by the injection of extra sodium cations into the cell; these cations can come from a wide variety of sources, such as chemical synapse
Chemical synapse
Chemical synapses are specialized junctions through which neurons signal to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous system. They are crucial to the biological computations that underlie...

s, sensory neuron
Sensory neuron
Sensory neurons are typically classified as the neurons responsible for converting external stimuli from the environment into internal stimuli. They are activated by sensory input , and send projections into the central nervous system that convey sensory information to the brain or spinal cord...

s or pacemaker potential
Pacemaker potential
In the pacemaking cells of the heart , the pacemaker potential is the slow, positive increase in voltage across the cell's membrane that occurs between the end of one action potential and the beginning of the next action potential...

s.

For a neuron at rest, there is a high concentration of sodium and chlorine ions in the extracellular fluid
Extracellular fluid
Extracellular fluid usually denotes all body fluid outside of cells. The remainder is called intracellular fluid.In some animals, including mammals, the extracellular fluid can be divided into two major subcompartments, interstitial fluid and blood plasma...

 compared to the intracellular fluid while there is a high concentration of potassium ions in the intracellular fluid compared to the extracellular fluid. This concentration gradient along with potassium leak channels present on the membrane of the neuron causes an efflux of potassium ions making the resting potential close to EK≈ –75 mV. The depolarization opens both the sodium and potassium channels in the membrane, allowing the ions to flow into and out of the axon, respectively. If the depolarization is small (say, increasing Vm from −70 mV to −60 mV), the outward potassium current overwhelms the inward sodium current and the membrane repolarizes back to its normal resting potential around −70 mV. However, if the depolarization is large enough, the inward sodium current increases more than the outward potassium current and a runaway condition (positive feedback
Positive feedback
Positive feedback is a process in which the effects of a small disturbance on a system include an increase in the magnitude of the perturbation. That is, A produces more of B which in turn produces more of A. In contrast, a system that responds to a perturbation in a way that reduces its effect is...

) results: the more inward current there is, the more Vm increases, which in turn further increases the inward current. A sufficiently strong depolarization (increase in Vm) causes the voltage-sensitive sodium channels to open; the increasing permeability to sodium drives Vm closer to the sodium equilibrium voltage ENa≈ +55 mV. The increasing voltage in turn causes even more sodium channels to open, which pushes Vm still further towards ENa. This positive feedback continues until the sodium channels are fully open and Vm is close to ENa. The sharp rise in Vm and sodium permeability correspond to the rising phase of the action potential.

The critical threshold voltage for this runaway condition is usually around −45 mV, but it depends on the recent activity of the axon. A membrane that has just fired an action potential cannot fire another one immediately, since the ion channels have not returned to their usual state. The period during which no new action potential can be fired is called the absolute refractory period. At longer times, after some but not all of the ion channels have recovered, the axon can be stimulated to produce another action potential, but only with a much stronger depolarization, e.g., −30 mV. The period during which action potentials are unusually difficult to evoke is called the relative refractory period.

Peak and falling phase


The positive feedback of the rising phase slows and comes to a halt as the sodium ion channels become maximally open. At the peak of the action potential, the sodium permeability is maximized and the membrane voltage Vm is nearly equal to the sodium equilibrium voltage ENa. However, the same raised voltage that opened the sodium channels initially also slowly shuts them off, by closing their pores; the sodium channels become inactivated. This lowers the membrane's permeability to sodium relative to potassium, driving the membrane voltage back towards the resting value. At the same time, the raised voltage opens voltage-sensitive potassium channels; the increase in the membrane's potassium permeability drives Vm towards EK. Combined, these changes in sodium and potassium permeability cause Vm to drop quickly, repolarizing the membrane and producing the "falling phase" of the action potential.

Afterhyperpolarization


The raised voltage opened many more potassium channels than usual, and some of these do not close right away when the membrane returns to its normal resting voltage. In addition, further potassium channels
SK channel
SK channels are a subfamily of Ca2+-activated K+ channels. They are so called because of their small single channel conductance, ~10 pS. SK channels are a type of ion channel allowing potassium cations to cross the cell membrane and are activated by an increase in the concentration of...

 open in response to the influx of calcium ions during the action potential. The potassium permeability of the membrane is transiently unusually high, driving the membrane voltage Vm even closer to the potassium equilibrium voltage EK. Hence, there is an undershoot or hyperpolarization
Hyperpolarization (biology)
Hyperpolarization is a change in a cell's membrane potential that makes it more negative. It is the opposite of a depolarization.Hyperpolarization is often caused by efflux of K+ through K+ channels, or influx of Cl– through Cl– channels. On the other hand, influx of cations, e.g...

, termed an afterhyperpolarization
Afterhyperpolarization
Afterhyperpolarization or AHP describes the hyperpolarization phase of a neuron's action potential where the cell's membrane potential falls below the normal resting potential. This is also commonly referred to as an action potential's undershoot phase...

 in technical language, that persists until the membrane potassium permeability returns to its usual value.

Refractory period


Each action potential is followed by a refractory period, which can be divided into an absolute refractory period, during which it is impossible to evoke another action potential, and then a relative refractory period, during which a stronger-than-usual stimulus is required. These two refractory periods are caused by changes in the state of sodium and potassium channel molecules. When closing after an action potential, sodium channels enter an "inactivated" state, in which they cannot be made to open regardless of the membrane potential—this gives rise to the absolute refractory period. Even after a sufficient number of sodium channels have transitioned back to their resting state, it frequently happens that a fraction of potassium channels remains open, making it difficult for the membrane potential to depolarize, and thereby giving rise to the relative refractory period. Because the density and subtypes of potassium channels may differ greatly between different types of neurons, the duration of the relative refractory period is highly variable.

The absolute refractory period is largely responsible for the unidirectional propagation of action potentials along axons. At any given moment, the patch of axon behind the actively spiking part is refractory, but the patch in front, not having been activated recently, is capable of being stimulated by the depolarization from the action potential.

Propagation




The action potential generated at the axon hillock propagates as a wave along the axon. The currents flowing inwards at a point on the axon during an action potential spread out along the axon, and depolarize the adjacent sections of its membrane. If sufficiently strong, this depolarization provokes a similar action potential at the neighboring membrane patches. This basic mechanism was demonstrated by Alan Lloyd Hodgkin
Alan Lloyd Hodgkin
Sir Alan Lloyd Hodgkin, OM, KBE, PRS was a British physiologist and biophysicist, who shared the 1963 Nobel Prize in Physiology or Medicine with Andrew Huxley and John Eccles....

 in 1937. After crushing or cooling nerve segments and thus blocking the action potentials, he showed that an action potential arriving on one side of the block could provoke another action potential on the other, provided that the blocked segment was sufficiently short.

Once an action potential has occurred at a patch of membrane, the membrane patch needs time to recover before it can fire again. At the molecular level, this absolute refractory period corresponds to the time required for the voltage-activated sodium channels to recover from inactivation, i.e., to return to their closed state. There are many types of voltage-activated potassium channels in neurons, some of them inactivate fast (A-type currents) and some of them inactivate slowly or not inactivate at all; this variability guarantees that there will be always an available source of current for repolarization, even if some of the potassium channels are inactivated because of preceding depolarization. On the other hand, all neuronal voltage-activated sodium channels inactivate within several millisecond during strong depolarization, thus making following depolarization impossible until a substantial fraction of sodium channels is not returned to their closed state. Although it limits the frequency of firing, the absolute refractory period ensures that the action potential moves in only one direction along an axon. The currents flowing in due to an action potential spread out in both directions along the axon. However, only the unfired part of the axon can respond with an action potential; the part that has just fired is unresponsive until the action potential is safely out of range and cannot restimulate that part. In the usual orthodromic conduction, the action potential propagates from the axon hillock towards the synaptic knobs (the axonal termini); propagation in the opposite direction—known as antidromic conduction—is very rare. However, if a laboratory axon is stimulated in its middle, both halves of the axon are "fresh", i.e., unfired; then two action potentials will be generated, one traveling towards the axon hillock and the other traveling towards the synaptic knobs.


Myelin and saltatory conduction


In order to enable fast and efficient transduction of electrical signals in the nervous system, certain neuronal axons are covered with myelin
Myelin
Myelin is a dielectric material that forms a layer, the myelin sheath, usually around only the axon of a neuron. It is essential for the proper functioning of the nervous system. Myelin is an outgrowth of a type of glial cell. The production of the myelin sheath is called myelination...

 sheaths. Myelin is a multilamellar membrane that enwraps the axon in segments separated by intervals known as nodes of Ranvier
Nodes of Ranvier
Myelin sheath gaps or nodes of Ranvier are the gaps formed between the myelin sheaths generated by different cells. A myelin sheath is a many-layered coating, largely composed of a fatty substance called myelin, that wraps around the axon of a neuron and very efficiently insulates it...

, is produced by specialized cells, Schwann cell
Schwann cell
Schwann cells or neurolemmocytes are the principal glia of the peripheral nervous system . Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory ensheathing cells, enteric glia and glia that reside at sensory nerve endings, such as the Pacinian corpuscle...

s exclusively in the peripheral nervous system
Peripheral nervous system
The peripheral nervous system consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain...

, and by oligodendrocyte
Oligodendrocyte
Oligodendrocytes , or oligodendroglia , are a type of brain cell. They are a variety of neuroglia. Their main function is the insulation of axons in the central nervous system of some vertebrates...

s exclusively in the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

. Myelin sheath reduces membrane capacitance and increases membrane resistance in the inter-node intervals, thus allowing a fast, saltatory movement of action potentials from node to node. Myelination is found mainly in vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...

s, but an analogous system has been discovered in a few invertebrates, such as some species of shrimp
Shrimp
Shrimp are swimming, decapod crustaceans classified in the infraorder Caridea, found widely around the world in both fresh and salt water. Adult shrimp are filter feeding benthic animals living close to the bottom. They can live in schools and can swim rapidly backwards. Shrimp are an important...

. Not all neurons in vertebrates are myelinated; for example, axons of the neurons comprising autonomous (vegetative) nervous system are not myelinated in general.

Myelin prevents ions from entering or leaving the axon along myelinated segments. As a general rule, myelination increases the conduction velocity of action potentials and makes them more energy-efficient. Whether saltatory or not, the mean conduction velocity of an action potential ranges from 1 m/s to over 100 m/s, and, in general, increases with axonal diameter.

Action potentials cannot propagate through the membrane in myelinated segments of the axon. However, the current is carried by the cytoplasm, which is sufficient to depolarize the first or second subsequent node of Ranvier. Instead, the ionic current from an action potential at one node of Ranvier provokes another action potential at the next node; this apparent "hopping" of the action potential from node to node is known as saltatory conduction
Saltatory conduction
Saltatory conduction is the propagation of action potentials along myelinated axons from one node of Ranvier to the next node, increasing the conduction velocity of action potentials without needing to increase the diameter of an axon.-Mechanism:Because the cytoplasm of the axon is electrically...

. Although the mechanism of saltatory conduction was suggested in 1925 by Ralph Lillie, the first experimental evidence for saltatory conduction came from Ichiji Tasaki
Ichiji Tasaki
Dr. Ichiji Tasaki was a Japanese biophysicist and physician involved in research relating to the electical impulses in the nervous system. He is credited with discovering the insulating function of the myelin sheath...

 and Taiji Takeuchi*
* and from Andrew Huxley
Andrew Huxley
Sir Andrew Fielding Huxley, OM, FRS is an English physiologist and biophysicist, who won the 1963 Nobel Prize in Physiology or Medicine for his experimental and mathematical work with Sir Alan Lloyd Hodgkin on the basis of nerve action potentials, the electrical impulses that enable the activity...

 and Robert Stämpfli.* By contrast, in unmyelinated axons, the action potential provokes another in the membrane immediately adjacent, and moves continuously down the axon like a wave.

Myelin has two important advantages: fast conduction speed and energy efficiency. For axons larger than a minimum diameter (roughly 1 micrometre
Micrometre
A micrometer , is by definition 1×10-6 of a meter .In plain English, it means one-millionth of a meter . Its unit symbol in the International System of Units is μm...

), myelination increases the conduction velocity of an action potential, typically tenfold. Conversely, for a given conduction velocity, myelinated fibers are smaller than their unmyelinated counterparts. For example, action potentials move at roughly the same speed (25 m/s) in a myelinated frog axon and an unmyelinated squid giant axon, but the frog axon has a roughly 30-fold smaller diameter and 1000-fold smaller cross-sectional area. Also, since the ionic currents are confined to the nodes of Ranvier, far fewer ions "leak" across the membrane, saving metabolic energy. This saving is a significant selective advantage
Natural selection
Natural selection is the nonrandom process by which biologic traits become either more or less common in a population as a function of differential reproduction of their bearers. It is a key mechanism of evolution....

, since the human nervous system uses approximately 20% of the body's metabolic energy.

The length of axons' myelinated segments is important to the success of saltatory conduction. They should be as long as possible to maximize the speed of conduction, but not so long that the arriving signal is too weak to provoke an action potential at the next node of Ranvier. In nature, myelinated segments are generally long enough for the passively propagated signal to travel for at least two nodes while retaining enough amplitude to fire an action potential at the second or third node. Thus, the safety factor of saltatory conduction is high, allowing transmission to bypass nodes in case of injury. However, action potentials may end prematurely in certain places where the safety factor is low, even in unmyelinated neurons; a common example is the branch point of an axon, where it divides into two axons.

Some diseases degrade myelin and impair saltatory conduction, reducing the conduction velocity of action potentials. The most well-known of these is multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...

, in which the breakdown of myelin impairs coordinated movement.

Cable theory


The flow of currents within an axon can be described quantitatively by cable theory
Cable theory
Classical cable theory uses mathematical models to calculate the flow of electric current along passive neuronal fibers particularly dendrites that receive synaptic inputs at different sites and times...

 and its elaborations, such as the compartmental model. Cable theory was developed in 1855 by Lord Kelvin
William Thomson, 1st Baron Kelvin
William Thomson, 1st Baron Kelvin OM, GCVO, PC, PRS, PRSE, was a mathematical physicist and engineer. At the University of Glasgow he did important work in the mathematical analysis of electricity and formulation of the first and second laws of thermodynamics, and did much to unify the emerging...

 to model the transatlantic telegraph cable and was shown to be relevant to neurons by Hodgkin
Alan Lloyd Hodgkin
Sir Alan Lloyd Hodgkin, OM, KBE, PRS was a British physiologist and biophysicist, who shared the 1963 Nobel Prize in Physiology or Medicine with Andrew Huxley and John Eccles....

 and Rushton
W. A. H. Rushton
William Albert Hugh Rushton FRS was professor of Physiology at Trinity College, Cambridge. His main interest lay in colour vision and his Principle of Univariance is of seminal importance in the study of perception....

 in 1946. In simple cable theory, the neuron is treated as an electrically passive, perfectly cylindrical transmission cable, which can be described by a partial differential equation
Partial differential equation
In mathematics, partial differential equations are a type of differential equation, i.e., a relation involving an unknown function of several independent variables and their partial derivatives with respect to those variables...




where V(x, t) is the voltage across the membrane at a time t and a position x along the length of the neuron, and where λ and τ are the characteristic length and time scales on which those voltages decay in response to a stimulus. Referring to the circuit diagram above, these scales can be determined from the resistances and capacitances per unit length



These time and length-scales can be used to understand the dependence of the conduction velocity on the diameter of the neuron in unmyelinated fibers. For example, the time-scale τ increases with both the membrane resistance rm and capacitance cm. As the capacitance increases, more charge must be transferred to produce a given transmembrane voltage (by the equation Q=CV
Capacitance
In electromagnetism and electronics, capacitance is the ability of a capacitor to store energy in an electric field. Capacitance is also a measure of the amount of electric potential energy stored for a given electric potential. A common form of energy storage device is a parallel-plate capacitor...

); as the resistance increases, less charge is transferred per unit time, making the equilibration slower. In similar manner, if the internal resistance per unit length ri is lower in one axon than in another (e.g., because the radius of the former is larger), the spatial decay length λ becomes longer and the conduction velocity of an action potential should increase. If the transmembrane resistance rm is increased, that lowers the average "leakage" current across the membrane, likewise causing λ to become longer, increasing the conduction velocity.

Chemical synapses


In general, action potentials that reach the synaptic knobs cause a neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

 to be released into the synaptic cleft. Neurotransmitters are small molecules that may open ion channels in the postsynaptic cell; most axons have the same neurotransmitter at all of their termini. The arrival of the action potential opens voltage-sensitive calcium channels in the presynaptic membrane; the influx of calcium causes vesicles
Synaptic vesicle
In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...

 filled with neurotransmitter to migrate to the cell's surface and release their contents
Exocytosis
Exocytosis , also known as 'The peni-cytosis', is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane...

 into the synaptic cleft. This complex process is inhibited by the neurotoxin
Neurotoxin
A neurotoxin is a toxin that acts specifically on nerve cells , usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue...

s tetanospasmin
Tetanospasmin
Tetanus toxin is an extremely potent neurotoxin produced by the vegetative cell of Clostridium tetani in anaerobic conditions, causing tetanus. It has no known function for clostridia in the soil environment where they are normally encountered. It is also called spasmogenic toxin, tetanospasmin or...

 and botulinum toxin
Botulinum toxin
Botulinum toxin is a protein produced by the bacterium Clostridium botulinum, and is considered the most powerful neurotoxin ever discovered. Botulinum toxin causes Botulism poisoning, a serious and life-threatening illness in humans and animals...

, which are responsible for tetanus
Tetanus
Tetanus is a medical condition characterized by a prolonged contraction of skeletal muscle fibers. The primary symptoms are caused by tetanospasmin, a neurotoxin produced by the Gram-positive, rod-shaped, obligate anaerobic bacterium Clostridium tetani...

 and botulism
Botulism
Botulism also known as botulinus intoxication is a rare but serious paralytic illness caused by botulinum toxin which is metabolic waste produced under anaerobic conditions by the bacterium Clostridium botulinum, and affecting a wide range of mammals, birds and fish...

, respectively.


Electrical synapses


Some synapses dispense with the "middleman" of the neurotransmitter, and connect the presynaptic and postsynaptic cells together. When an action potential reaches such a synapse, the ionic currents flowing into the presynaptic cell can cross the barrier of the two cell membranes and enter the postsynaptic cell through pores known as connexin
Connexin
Connexins, or gap junction proteins, are a family of structurally-related transmembrane proteins that assemble to form vertebrate gap junctions . Each gap junction is composed of two hemichannels, or connexons, which are themselves each constructed out of six connexin molecules...

s. Thus, the ionic currents of the presynaptic action potential can directly stimulate the postsynaptic cell. Electrical synapses allow for faster transmission because they do not require the slow diffusion of neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

s across the synaptic cleft. Hence, electrical synapses are used whenever fast response and coordination of timing are crucial, as in escape reflex
Escape reflex
Escape reflex, a kind of escape response, is a simple reflectory reaction in response to stimuli indicative of danger, that initiates an escape motion of an animal....

es, the retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...

 of vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...

s, and the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...

.

Neuromuscular junctions


A special case of a chemical synapse is the neuromuscular junction
Neuromuscular junction
A neuromuscular junction is the synapse or junction of the axon terminal of a motor neuron with the motor end plate, the highly-excitable region of muscle fiber plasma membrane responsible for initiation of action potentials across the muscle's surface, ultimately causing the muscle to contract...

, in which the axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....

 of a motor neuron
Motor neuron
In vertebrates, the term motor neuron classically applies to neurons located in the central nervous system that project their axons outside the CNS and directly or indirectly control muscles...

 terminates on a muscle fiber. In such cases, the released neurotransmitter is acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...

, which binds to the acetylcholine receptor, an integral membrane protein in the membrane (the sarcolemma
Sarcolemma
The sarcolemma is the cell membrane of a muscle cell . It consists of a true cell membrane, called the plasma membrane, and an outer coat made up of a thin layer of polysaccharide material that contains numerous thin collagen fibrils...

) of the muscle fiber. However, the acetylcholine does not remain bound; rather, it dissociates and is hydrolyzed
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...

 by the enzyme, acetylcholinesterase
Acetylcholinesterase
"Acetylcholinesterase, also known as AChE or acetylcholine acetylhydrolase, is an enzyme that degrades the neurotransmitter acetylcholine, producing choline and an acetate group. It is mainly found at neuromuscular junctions and cholinergic nervous system, where its activity serves to terminate...

, located in the synapse. This enzyme quickly reduces the stimulus to the muscle, which allows the degree and timing of muscular contraction to be regulated delicately. Some poisons inactivate acetylcholinesterase to prevent this control, such as the nerve agent
Nerve agent
Nerve agents are a class of phosphorus-containing organic chemicals that disrupt the mechanism by which nerves transfer messages to organs...

s sarin
Sarin
Sarin, or GB, is an organophosphorus compound with the formula [2CHO]CH3PF. It is a colorless, odorless liquid, which is used as a chemical weapon. It has been classified as a weapon of mass destruction in UN Resolution 687...

 and tabun
Tabun (nerve agent)
Tabun or GA is an extremely toxic chemical substance. It is a clear, colorless, and tasteless liquid with a faint fruity odor. It is classified as a nerve agent because it fatally interferes with normal functioning of the mammalian nervous system...

, and the insecticides diazinon
Diazinon
Diazinon , a colorless to dark brown liquid, is a thiophosphoric acid ester developed in 1952 by Ciba-Geigy, a Swiss chemical company...

 and malathion
Malathion
Malathion is an organophosphate parasympathomimetic which binds irreversibly to cholinesterase. Malathion is an insecticide of relatively low human toxicity, however one recent study has shown that children with higher levels of organophosphate pesticide metabolites in their urine are more likely...

.

Cardiac action potentials


The cardiac action potential differs from the neuronal action potential by having an extended plateau, in which the membrane is held at a high voltage for a few hundred milliseconds prior to being repolarized by the potassium current as usual. This plateau is due to the action of slower calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

 channels opening and holding the membrane voltage near their equilibrium potential even after the sodium channels have inactivated.

The cardiac action potential plays an important role in coordinating the contraction of the heart. The cardiac cells of the sinoatrial node
Sinoatrial node
The sinoatrial node is the impulse-generating tissue located in the right atrium of the heart, and thus the generator of normal sinus rhythm. It is a group of cells positioned on the wall of the right atrium, near the entrance of the superior vena cava...

 provide the pacemaker potential
Pacemaker potential
In the pacemaking cells of the heart , the pacemaker potential is the slow, positive increase in voltage across the cell's membrane that occurs between the end of one action potential and the beginning of the next action potential...

 that synchronizes the heart. The action potentials of those cells propagate to and through the atrioventricular node
Atrioventricular node
The atrioventricular node is a part of the electrical control system of the heart that coordinates heart rate. It electrically connects atrial and ventricular chambers...

 (AV node), which is normally the only conduction pathway between the atria and the ventricles
Ventricle (heart)
In the heart, a ventricle is one of two large chambers that collect and expel blood received from an atrium towards the peripheral beds within the body and lungs. The Atria primes the Pump...

. Action potentials from the AV node travel through the bundle of His
Bundle of His
The bundle of His, known as the AV bundle or atrioventricular bundle, is a collection of heart muscle cells specialized for electrical conduction that transmits the electrical impulses from the AV node to the point of the apex of the fascicular branches...

 and thence to the Purkinje fibers.Note that these Purkinje fibers are muscle fibers and not related to the Purkinje cell
Purkinje cell
For the cells of the electrical conduction system of the heart, see Purkinje fibersPurkinje cells, or Purkinje neurons , are a class of GABAergic neurons located in the cerebellar cortex...

s, which are neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

s found in the cerebellum
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...

.
Conversely, anomalies in the cardiac action potential—whether due to a congenital mutation or injury—can lead to human pathologies, especially arrhythmias. Several anti-arrhythmia drugs act on the cardiac action potential, such as quinidine
Quinidine
Quinidine is a pharmaceutical agent that acts as a class I antiarrhythmic agent in the heart. It is a stereoisomer of quinine, originally derived from the bark of the cinchona tree.-Mechanism:...

, lidocaine
Lidocaine
Lidocaine , Xylocaine, or lignocaine is a common local anesthetic and antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic or as a local anesthetic for minor surgery.- History :Lidocaine, the first amino...

, beta blocker
Beta blocker
Beta blockers or beta-adrenergic blocking agents, beta-adrenergic antagonists, beta-adrenoreceptor antagonists or beta antagonists, are a class of drugs used for various indications. They are particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction ,...

s, and verapamil
Verapamil
Verapamil is an L-type calcium channel blocker of the phenylalkylamine class. It has been used in the treatment of hypertension, angina pectoris, cardiac arrhythmia, and most recently, cluster headaches. It is also an effective preventive medication for migraine...

.

Muscular action potentials


The action potential in a normal skeletal muscle cell is similar to the action potential in neurons. Action potentials result from the depolarization of the cell membrane (the sarcolemma
Sarcolemma
The sarcolemma is the cell membrane of a muscle cell . It consists of a true cell membrane, called the plasma membrane, and an outer coat made up of a thin layer of polysaccharide material that contains numerous thin collagen fibrils...

), which opens voltage-sensitive sodium channels; these become inactivated and the membrane is repolarized through the outward current of potassium ions. The resting potential prior to the action potential is typically −90mV, somewhat more negative than typical neurons. The muscle action potential lasts roughly 2–4 ms, the absolute refractory period is roughly 1–3 ms, and the conduction velocity along the muscle is roughly 5 m/s. The action potential releases calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

 ions that free up the tropomyosin
Tropomyosin
Tropomyosin is an actin-binding protein that regulates actin mechanics. It is important, among other things, for muscle contraction. Tropomyosin, along with the troponin complex, associate with actin in muscle fibers and regulate muscle contraction by regulating the binding of myosin...

 and allow the muscle to contract. Muscle action potentials are provoked by the arrival of a pre-synaptic neuronal action potential at the neuromuscular junction
Neuromuscular junction
A neuromuscular junction is the synapse or junction of the axon terminal of a motor neuron with the motor end plate, the highly-excitable region of muscle fiber plasma membrane responsible for initiation of action potentials across the muscle's surface, ultimately causing the muscle to contract...

, which is a common target for neurotoxin
Neurotoxin
A neurotoxin is a toxin that acts specifically on nerve cells , usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue...

s.

Plant action potentials


Plant and fungal cells  are also electrically excitable. The fundamental difference to animal action potentials is, that the depolarization in plant cells is not accomplished by an uptake of positive sodium ions, but by release of negative chloride ions. Together with the following release of positive potassium ions, which is common to plant and animal action potentials, the action potential in plants infers, therefore, an osmotic loss of salt (KCl), whereas the animal action potential is osmotically neutral, when equal amounts of entering sodium and leaving potassium cancel each other osmotically. The interaction of electrical and osmotic relations in plant cells indicates an osmotic function of electrical excitability in the common, unicellular ancestors of plants and animals under changing salinity conditions, whereas the present function of rapid signal transmission is seen as a younger accomplishment of metazoan cells in a more stable osmotic environment. It must be assumed that the familiar signalling function of action potentials in some vascular plants (e.g. Mimosa pudica
Mimosa pudica
Mimosa pudica , is a creeping annual or perennial herb often grown for its curiosity value: the compound leaves fold inward and droop when touched or shaken, re-opening minutes later...

), arose independently from that in metazoan excitable cells.

Taxonomic distribution and evolutionary advantages


Action potentials are found throughout multicellular organism
Multicellular organism
Multicellular organisms are organisms that consist of more than one cell, in contrast to single-celled organisms. Most life that can be seen with the the naked eye is multicellular, as are all animals and land plants.-Evolutionary history:Multicellularity has evolved independently dozens of times...

s, including plant
Plant
Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...

s, invertebrate
Invertebrate
An invertebrate is an animal without a backbone. The group includes 97% of all animal species – all animals except those in the chordate subphylum Vertebrata .Invertebrates form a paraphyletic group...

s such as insect
Insect
Insects are a class of living creatures within the arthropods that have a chitinous exoskeleton, a three-part body , three pairs of jointed legs, compound eyes, and two antennae...

s, and vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...

s such as reptile
Reptile
Reptiles are members of a class of air-breathing, ectothermic vertebrates which are characterized by laying shelled eggs , and having skin covered in scales and/or scutes. They are tetrapods, either having four limbs or being descended from four-limbed ancestors...

s and mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...

s. Sponges seem to be the main phylum
Phylum
In biology, a phylum The term was coined by Georges Cuvier from Greek φῦλον phylon, "race, stock," related to φυλή phyle, "tribe, clan." is a taxonomic rank below kingdom and above class. "Phylum" is equivalent to the botanical term division....

 of multicellular eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...

s that does not transmit action potentials, although some studies have suggested that these organisms have a form of electrical signaling, too. The resting potential, as well as the size and duration of the action potential, have not varied much with evolution, although the conduction velocity does vary dramatically with axonal diameter and myelination.

Comparison of action potentials (APs) from a representative cross-section of animals
Animal Cell type Resting potential (mV) AP increase (mV) AP duration (ms) Conduction speed (m/s)
Squid (Loligo) Giant axon −60 120 0.75 35
Earthworm (Lumbricus) Median giant fiber −70 100 1.0 30
Cockroach (Periplaneta) Giant fiber −70 80–104 0.4 10
Frog (Rana) Sciatic nerve axon −60 to −80 110–130 1.0 7–30
Cat (Felis) Spinal motor neuron −55 to −80 80–110 1–1.5 30–120



Given its conservation throughout evolution, the action potential seems to confer evolutionary advantages. One function of action potentials is rapid, long-range signaling within the organism; the conduction velocity can exceed 110 m/s, which is one-third the speed of sound
Speed of sound
The speed of sound is the distance travelled during a unit of time by a sound wave propagating through an elastic medium. In dry air at , the speed of sound is . This is , or about one kilometer in three seconds or approximately one mile in five seconds....

. For comparison, a hormone molecule carried in the bloodstream moves at roughly 8 m/s in large arteries. Part of this function is the tight coordination of mechanical events, such as the contraction of the heart. A second function is the computation associated with its generation. Being an all-or-none signal that does not decay with transmission distance, the action potential has similar advantages to digital electronics. The integration of various dendritic signals at the axon hillock and its thresholding to form a complex train of action potentials is another form of computation, one that has been exploited biologically to form central pattern generator
Central pattern generator
Central pattern generators are neural networks that produce rhythmic patterned outputs without sensory feedback. CPGs have been shown to produce rhythmic outputs resembling normal "rhythmic motor pattern production" even in isolation from motor and sensory feedback from limbs and other muscle...

s and mimicked in artificial neural network
Artificial neural network
An artificial neural network , usually called neural network , is a mathematical model or computational model that is inspired by the structure and/or functional aspects of biological neural networks. A neural network consists of an interconnected group of artificial neurons, and it processes...

s.

Experimental methods


The study of action potentials has required the development of new experimental methods. The initial work, prior to 1955, focused on three goals: isolating signals from single neurons or axons, developing fast, sensitive electronics, and shrinking electrode
Electrode
An electrode is an electrical conductor used to make contact with a nonmetallic part of a circuit...

s enough that the voltage inside a single cell could be recorded.

The first problem was solved by studying the giant axons found in the neurons of the squid
Squid
Squid are cephalopods of the order Teuthida, which comprises around 300 species. Like all other cephalopods, squid have a distinct head, bilateral symmetry, a mantle, and arms. Squid, like cuttlefish, have eight arms arranged in pairs and two, usually longer, tentacles...

 genus Loligo
Loligo
Loligo is a genus of squids and one of the most representative and widely distributed groups of myopsid squids.The genus was first described by Jean Baptiste Lamarck in 1798. However, the name had been used earlier than Lamarck and might even have been used by Pliny...

. These axons are so large in diameter (roughly 1 mm, or 100-fold larger than a typical neuron) that they can be seen with the naked eye, making them easy to extract and manipulate. However, the Loligo axons are not representative of all excitable cells, and numerous other systems with action potentials have been studied.

The second problem was addressed with the crucial development of the voltage clamp
Voltage clamp
The voltage clamp is used by electrophysiologists to measure the ion currents across the membrane of excitable cells, such as neurons, while holding the membrane voltage at a set level. Cell membranes of excitable cells contain many different kinds of ion channels, some of which are voltage gated...

, which permitted experimenters to study the ionic currents underlying an action potential in isolation, and eliminated a key source of electronic noise
Electronic noise
Electronic noise is a random fluctuation in an electrical signal, a characteristic of all electronic circuits. Noise generated by electronic devices varies greatly, as it can be produced by several different effects...

, the current IC associated with the capacitance
Capacitance
In electromagnetism and electronics, capacitance is the ability of a capacitor to store energy in an electric field. Capacitance is also a measure of the amount of electric potential energy stored for a given electric potential. A common form of energy storage device is a parallel-plate capacitor...

 C of the membrane. Since the current equals C times the rate of change of the transmembrane voltage Vm, the solution was to design a circuit that kept Vm fixed (zero rate of change) regardless of the currents flowing across the membrane. Thus, the current required to keep Vm at a fixed value is a direct reflection of the current flowing through the membrane. Other electronic advances included the use of Faraday cage
Faraday cage
A Faraday cage or Faraday shield is an enclosure formed by conducting material or by a mesh of such material. Such an enclosure blocks out external static and non-static electric fields...

s and electronics with high input impedance
Input impedance
The input impedance of an electrical network is the equivalent impedance "seen" by a power source connected to that network. If the source provides known voltage and current, such impedance can be calculated using Ohm's Law...

, so that the measurement itself did not affect the voltage being measured.

The third problem, that of obtaining electrodes small enough to record voltages within a single axon without perturbing it, was solved in 1949 with the invention of the glass micropipette electrode, which was quickly adopted by other researchers. Refinements of this method are able to produce electrode tips that are as fine as 100 Å
Ångström
The angstrom or ångström, is a unit of length equal to 1/10,000,000,000 of a meter . Its symbol is the Swedish letter Å....

 (10 nm
Nanometre
A nanometre is a unit of length in the metric system, equal to one billionth of a metre. The name combines the SI prefix nano- with the parent unit name metre .The nanometre is often used to express dimensions on the atomic scale: the diameter...

), which also confers high input impedance. Action potentials may also be recorded with small metal electrodes placed just next to a neuron, with neurochip
Neurochip
A neurochip is a chip that is designed for the interaction with neuronal cells.- Formation :It is made of silicon that is doped in such a way that it contains EOSFETs that can sense the electrical activity of the neurons in the above-standing physiological electrolyte solution...

s containing EOSFET
EOSFET
An EOSFET or electrolyte-oxide-semiconductor field effect transistor is a FET, like a MOSFET, but with the metal replaced by electrolyte solution for the detection of neuronal activity. Many EOSFETs are integrated in a neurochip....

s, or optically with dyes that are sensitive to Ca2+
Calcium imaging
Calcium imaging is a scientific technique usually carried out in research which is designed to show the calcium status of a tissue or medium....

 or to voltage.*

While glass micropipette electrodes measure the sum of the currents passing through many ion channels, studying the electrical properties of a single ion channel became possible in the 1970s with the development of the patch clamp
Patch clamp
The patch clamp technique is a laboratory technique in electrophysiology that allows the study of single or multiple ion channels in cells. The technique can be applied to a wide variety of cells, but is especially useful in the study of excitable cells such as neurons, cardiomyocytes, muscle...

 by Erwin Neher
Erwin Neher
Erwin Neher is a German biophysicist.Erwin Neher studied physics at the Technical University of Munich from 1963 to 1966. In 1966, He was awarded a Fulbright Scholarship to study in the US...

 and Bert Sakmann
Bert Sakmann
-External links:*...

. For this they were awarded the Nobel Prize in Physiology or Medicine
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...

 in 1991. Patch-clamping verified that ionic channels have discrete states of conductance, such as open, closed and inactivated.

Optical imaging
Optical imaging
Optical imaging is an imaging technique.Optics usually describes the behavior of visible, ultraviolet, and infrared light used in imaging.Because light is an electromagnetic wave, similar phenomena occur in X-rays, microwaves, radio waves. Chemical imaging or molecular imaging involves inference...

 technologies have been developed in recent years to measure action potentials, either via simultaneous multisite recordings or with ultra spatial resolution. Using voltage-sensitive dyes, action potentials have been optically recorded from a tiny patch of cardiomyocyte membrane.

Neurotoxins


Several neurotoxin
Neurotoxin
A neurotoxin is a toxin that acts specifically on nerve cells , usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue...

s, both natural and synthetic, are designed to block the action potential. Tetrodotoxin
Tetrodotoxin
Tetrodotoxin, also known as "tetrodox" and frequently abbreviated as TTX, sometimes colloquially referred to as "zombie powder" by those who practice Vodou, is a potent neurotoxin with no known antidote. There have been successful tests of a possible antidote in mice, but further tests must be...

 from the pufferfish
Pufferfish
Tetraodontidae is a family of primarily marine and estuarine fish of the Tetraodontiformes order. The family includes many familiar species which are variously called pufferfish, balloonfish, blowfish, bubblefish, globefish, swellfish, toadfish, toadies, honey toads, sugar toads, and sea squab...

 and saxitoxin
Saxitoxin
Saxitoxin is a neurotoxin naturally produced by certain species of marine dinoflagellates and cyanobacteria Saxitoxin (STX) is a neurotoxin naturally produced by certain species of marine dinoflagellates (Alexandrium sp., Gymnodinium sp., Pyrodinium sp.) and cyanobacteria Saxitoxin (STX) is a...

 from the Gonyaulax
Gonyaulax
Gonyaulax is a genus of Alveolata. They undergo rapid multiplication and they make the sea appear red. They produce a potent toxin known as Saxitoxin which affects nerve impulses and can lead to paralysis of muscles and may eventually end in asphyxiation.Members are covered by closely fitting...

 (the dinoflagellate
Dinoflagellate
The dinoflagellates are a large group of flagellate protists. Most are marine plankton, but they are common in fresh water habitats as well. Their populations are distributed depending on temperature, salinity, or depth...

 genus responsible for "red tide
Paralytic shellfish poisoning
Paralytic shellfish poisoning is one of the four recognized syndromes of shellfish poisoning, which share some common features and are primarily associated with bivalve mollusks . These shellfish are filter feeders and, therefore, accumulate toxins produced by microscopic algae, such as...

s") block action potentials by inhibiting the voltage-sensitive sodium channel;*
* similarly, dendrotoxin
Dendrotoxin
Dendrotoxins are a class of neurotoxins produced by mamba snakes that block particular subtypes of voltage-gated potassium channels in neurons, thereby enhancing the release of acetylcholine at neuromuscular junctions...

 from the black mamba
Mamba
Mambas, of the genus Dendroaspis , are a group of highly venomous, fast-moving land-dwelling snakes of Africa. They belong to the family of Elapidae which includes cobras, coral snakes, taipans, brown snakes, tiger snakes, death adders, kraits and, debatably, sea snakes...

 snake inhibits the voltage-sensitive potassium channel. Such inhibitors of ion channels serve an important research purpose, by allowing scientists to "turn off" specific channels at will, thus isolating the other channels' contributions; they can also be useful in purifying ion channels by affinity chromatography
Affinity chromatography
Affinity chromatography is a method of separating biochemical mixtures and based on a highly specific interaction such as that between antigen and antibody, enzyme and substrate, or receptor and ligand.-Uses:Affinity chromatography can be used to:...

 or in assaying their concentration. However, such inhibitors also make effective neurotoxins, and have been considered for use as chemical weapon
Chemical warfare
Chemical warfare involves using the toxic properties of chemical substances as weapons. This type of warfare is distinct from Nuclear warfare and Biological warfare, which together make up NBC, the military acronym for Nuclear, Biological, and Chemical...

s. Neurotoxins aimed at the ion channels of insects have been effective insecticide
Insecticide
An insecticide is a pesticide used against insects. They include ovicides and larvicides used against the eggs and larvae of insects respectively. Insecticides are used in agriculture, medicine, industry and the household. The use of insecticides is believed to be one of the major factors behind...

s; one example is the synthetic permethrin
Permethrin
Permethrin is a common synthetic chemical, widely used as an insecticide, acaricide, and insect repellent. It belongs to the family of synthetic chemicals called pyrethroids and functions as a neurotoxin, affecting neuron membranes by prolonging sodium channel activation. It is not known to...

, which prolongs the activation of the sodium channels involved in action potentials. The ion channels of insects are sufficiently different from their human counterparts that there are few side effects in humans. Many other neurotoxins interfere with the transmission of the action potential's effects at the synapses
Chemical synapse
Chemical synapses are specialized junctions through which neurons signal to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous system. They are crucial to the biological computations that underlie...

, especially at the neuromuscular junction
Neuromuscular junction
A neuromuscular junction is the synapse or junction of the axon terminal of a motor neuron with the motor end plate, the highly-excitable region of muscle fiber plasma membrane responsible for initiation of action potentials across the muscle's surface, ultimately causing the muscle to contract...

.

History


The role of electricity in the nervous systems of animals was first observed in dissected frog
Frog
Frogs are amphibians in the order Anura , formerly referred to as Salientia . Most frogs are characterized by a short body, webbed digits , protruding eyes and the absence of a tail...

s by Luigi Galvani
Luigi Galvani
Luigi Aloisio Galvani was an Italian physician and physicist who lived and died in Bologna. In 1791, he discovered that the muscles of dead frogs legs twitched when struck by a spark...

, who studied it from 1791 to 1797. Galvani's results stimulated Alessandro Volta
Alessandro Volta
Count Alessandro Giuseppe Antonio Anastasio Gerolamo Umberto Volta was a Lombard physicist known especially for the invention of the battery in 1800.-Early life and works:...

 to develop the Voltaic pile
Voltaic pile
A voltaic pile is a set of individual Galvanic cells placed in series. The voltaic pile, invented by Alessandro Volta in 1800, was the first electric battery...

—the earliest-known electric battery
Battery (electricity)
An electrical battery is one or more electrochemical cells that convert stored chemical energy into electrical energy. Since the invention of the first battery in 1800 by Alessandro Volta and especially since the technically improved Daniell cell in 1836, batteries have become a common power...

—with which he studied animal electricity (such as electric eel
Electric eel
The electric eel , is an electric fish, and the only species of the genus Electrophorus. It is capable of generating powerful electric shocks, of up to six hundred volts, which it uses for both hunting and self-defense. It is an apex predator in its South American range...

s) and the physiological responses to applied direct-current
Direct current
Direct current is the unidirectional flow of electric charge. Direct current is produced by such sources as batteries, thermocouples, solar cells, and commutator-type electric machines of the dynamo type. Direct current may flow in a conductor such as a wire, but can also flow through...

 voltage
Voltage
Voltage, otherwise known as electrical potential difference or electric tension is the difference in electric potential between two points — or the difference in electric potential energy per unit charge between two points...

s.

Scientists of the 19th century studied the propagation of electrical signals in whole nerve
Nerve
A peripheral nerve, or simply nerve, is an enclosed, cable-like bundle of peripheral axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons. Nerves are found only in the peripheral nervous system...

s (i.e., bundles of neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

s) and demonstrated that nervous tissue was made up of cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

, instead of an interconnected network of tubes (a reticulum).*
* Carlo Matteucci
Carlo Matteucci
Carlo Matteucci was an Italian physicist and neurophysiologist who was a pioneer in the study of bioelectricity.-Biography:...

 followed up Galvani's studies and demonstrated that cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

s had a voltage across them and could produce direct current
Direct current
Direct current is the unidirectional flow of electric charge. Direct current is produced by such sources as batteries, thermocouples, solar cells, and commutator-type electric machines of the dynamo type. Direct current may flow in a conductor such as a wire, but can also flow through...

. Matteucci's work inspired the German physiologist, Emil du Bois-Reymond
Emil du Bois-Reymond
Emil du Bois-Reymond was a German physician and physiologist, the discoverer of nerve action potential, and the father of experimental electrophysiology.-Life:...

, who discovered the action potential in 1848. The conduction velocity of action potentials was first measured in 1850 by du Bois-Reymond's friend, Hermann von Helmholtz
Hermann von Helmholtz
Hermann Ludwig Ferdinand von Helmholtz was a German physician and physicist who made significant contributions to several widely varied areas of modern science...

. To establish that nervous tissue is made up of discrete cells, the Spanish physician Santiago Ramón y Cajal
Santiago Ramón y Cajal
Santiago Ramón y Cajal ForMemRS was a Spanish pathologist, histologist, neuroscientist, and Nobel laureate. His pioneering investigations of the microscopic structure of the brain were original: he is considered by many to be the father of modern neuroscience...

 and his students used a stain developed by Camillo Golgi
Camillo Golgi
Camillo Golgi was an Italian physician, pathologist, scientist, and Nobel laureate.-Biography:Camillo Golgi was born in the village of Corteno, Lombardy, then part of the Austrian Empire. The village is now named Corteno Golgi in his honour. His father was a physician and district medical officer...

 to reveal the myriad shapes of neurons, which they rendered painstakingly. For their discoveries, Golgi and Ramón y Cajal were awarded the 1906 Nobel Prize in Physiology
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...

. Their work resolved a long-standing controversy in the neuroanatomy
Neuroanatomy
Neuroanatomy is the study of the anatomy and organization of the nervous system. In contrast to animals with radial symmetry, whose nervous system consists of a distributed network of cells, animals with bilateral symmetry have segregated, defined nervous systems, and thus we can begin to speak of...

 of the 19th century; Golgi himself had argued for the network model of the nervous system.

The 20th century was a golden era for electrophysiology. In 1902 and again in 1912, Julius Bernstein
Julius Bernstein
Julius Bernstein was a German physiologist who was born in Berlin. He studied medicine at the University of Breslau under Rudolf Heidenhain, and at the University of Berlin under Emil Du Bois-Reymond...

 advanced the hypothesis that the action potential resulted from a change in the permeability
Permeation
Permeation, in physics and engineering, is the penetration of a permeate through a solid, and is related to a material's intrinsic permeability...

 of the axonal membrane to ions.* Bernstein's hypothesis was confirmed by Ken Cole
Kenneth Stewart Cole
Kenneth Stewart Cole was an American biophysicist described by his peers as "a pioneer in the application of physical science to biology". Cole was awarded the National Medal of Science in 1967.-Biography:...

 and Howard Curtis, who showed that membrane conductance increases during an action potential. In 1907, Louis Lapicque
Louis Lapicque
Louis Lapicque was a French neuroscientist who was very influential in the early 20th century. One of his main contributions was to propose the integrate and fire model of the neuron in a seminal article published in 1907...

 suggested that the action potential was generated as a threshold was crossed, what would be later shown as a product of the dynamical system
Dynamical system
A dynamical system is a concept in mathematics where a fixed rule describes the time dependence of a point in a geometrical space. Examples include the mathematical models that describe the swinging of a clock pendulum, the flow of water in a pipe, and the number of fish each springtime in a...

s of ionic conductances. In 1949, Alan Hodgkin
Alan Lloyd Hodgkin
Sir Alan Lloyd Hodgkin, OM, KBE, PRS was a British physiologist and biophysicist, who shared the 1963 Nobel Prize in Physiology or Medicine with Andrew Huxley and John Eccles....

 and Bernard Katz
Bernard Katz
Sir Bernard Katz, FRS was a German-born biophysicist, noted for his work on nerve biochemistry. He shared the Nobel Prize in physiology or medicine in 1970 with Julius Axelrod and Ulf von Euler...

 refined Bernstein's hypothesis by considering that the axonal membrane might have different permeabilities to different ions; in particular, they demonstrated the crucial role of the sodium permeability for the action potential. This line of research culminated in the five 1952 papers of Hodgkin, Katz and Andrew Huxley
Andrew Huxley
Sir Andrew Fielding Huxley, OM, FRS is an English physiologist and biophysicist, who won the 1963 Nobel Prize in Physiology or Medicine for his experimental and mathematical work with Sir Alan Lloyd Hodgkin on the basis of nerve action potentials, the electrical impulses that enable the activity...

, in which they applied the voltage clamp
Voltage clamp
The voltage clamp is used by electrophysiologists to measure the ion currents across the membrane of excitable cells, such as neurons, while holding the membrane voltage at a set level. Cell membranes of excitable cells contain many different kinds of ion channels, some of which are voltage gated...

 technique to determine the dependence of the axonal membrane's permeabilities to sodium and potassium ions on voltage and time, from which they were able to reconstruct the action potential quantitatively.*
*
*
* Hodgkin and Huxley correlated the properties of their mathematical model with discrete ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...

s that could exist in several different states, including "open", "closed", and "inactivated". Their hypotheses were confirmed in the mid-1970s and 1980s by Erwin Neher
Erwin Neher
Erwin Neher is a German biophysicist.Erwin Neher studied physics at the Technical University of Munich from 1963 to 1966. In 1966, He was awarded a Fulbright Scholarship to study in the US...

 and Bert Sakmann
Bert Sakmann
-External links:*...

, who developed the technique of patch clamp
Patch clamp
The patch clamp technique is a laboratory technique in electrophysiology that allows the study of single or multiple ion channels in cells. The technique can be applied to a wide variety of cells, but is especially useful in the study of excitable cells such as neurons, cardiomyocytes, muscle...

ing to examine the conductance states of individual ion channels.*
* In the 21st century, researchers are beginning to understand the structural basis for these conductance states and for the selectivity of channels for their species of ion, through the atomic-resolution crystal structures
X-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...

,*
* fluorescence distance measurements*
* and cryo-electron microscopy
Cryo-electron microscopy
Cryo-electron microscopy , or electron cryomicroscopy, is a form of transmission electron microscopy where the sample is studied at cryogenic temperatures...

 studies.*

Julius Bernstein was also the first to introduce the Nernst equation
Nernst equation
In electrochemistry, the Nernst equation is an equation that can be used to determine the equilibrium reduction potential of a half-cell in an electrochemical cell. It can also be used to determine the total voltage for a full electrochemical cell...

 for resting potential
Resting potential
The relatively static membrane potential of quiescent cells is called the resting membrane potential , as opposed to the specific dynamic electrochemical phenomena called action potential and graded membrane potential....

 across the membrane; this was generalized by David E. Goldman
David E. Goldman
David E. Goldman was a scientist famous for the Goldman equation which he derived for his doctorate degree at Columbia University....

 to the eponymous Goldman equation
Goldman equation
The Goldman–Hodgkin–Katz voltage equation, more commonly known as the Goldman equation is used in cell membrane physiology to determine the equilibrium potential across a cell's membrane taking into account all of the ions that are permeant through that membrane.The discoverers of this are David E...

 in 1943. The sodium–potassium pump
Na+/K+-ATPase
Na+/K+-ATPase is an enzyme located in the plasma membrane in all animals.- Sodium-potassium pumps :Active transport is responsible for cells containing relatively high...

 was identified in 1957 and its properties gradually elucidated, culminating in the determination of its atomic-resolution structure by X-ray crystallography
X-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...

. The crystal structures of related ionic pumps have also been solved, giving a broader view of how these molecular machines work.

Quantitative models


Mathematical and computational models are essential for understanding the action potential, and offer predictions that may be tested against experimental data, providing a stringent test of a theory. The most important and accurate of these models is the Hodgkin–Huxley model, which describes the action potential by a coupled set of four ordinary differential equation
Ordinary differential equation
In mathematics, an ordinary differential equation is a relation that contains functions of only one independent variable, and one or more of their derivatives with respect to that variable....

s (ODEs). Although the Hodgkin–Huxley model may be a simplification of a realistic nervous membrane as it exists in nature, its complexity has inspired several even-more-simplified models, such as the Morris–Lecar model and the FitzHugh–Nagumo model
FitzHugh–Nagumo model
The FitzHugh–Nagumo model, named after Richard FitzHugh who suggested the system in 1961 and J. Nagumo et al. who created the equivalent circuit the following year, describes a prototype of an excitable system ....

,* both of which have only two coupled ODEs. The properties of the Hodgkin–Huxley and FitzHugh–Nagumo models and their relatives, such as the Bonhoeffer–van der Pol model,*
*
*
* have been well-studied within mathematics,*
*
*
* computation* and electronics. More modern research has focused on larger and more integrated systems; by joining action-potential models with models of other parts of the nervous system (such as dendrites and synapses), researches can study neural computation
Neural Computation
Neural Computation is a peer-reviewed academic journal covering aspects of neural computation. Articles highlight problems and techniques in modeling the brain, and in the design and construction of neurally-inspired information processing systems. Neural Computation was founded in 1989 and is...

 and simple reflex
Reflex
A reflex action, also known as a reflex, is an involuntary and nearly instantaneous movement in response to a stimulus. A true reflex is a behavior which is mediated via the reflex arc; this does not apply to casual uses of the term 'reflex'.-See also:...

es, such as escape reflex
Escape reflex
Escape reflex, a kind of escape response, is a simple reflectory reaction in response to stimuli indicative of danger, that initiates an escape motion of an animal....

es and others controlled by central pattern generator
Central pattern generator
Central pattern generators are neural networks that produce rhythmic patterned outputs without sensory feedback. CPGs have been shown to produce rhythmic outputs resembling normal "rhythmic motor pattern production" even in isolation from motor and sensory feedback from limbs and other muscle...

s.

See also


  • Bursting
    Bursting
    Bursting is an extremely diverse general phenomenon of the activation patterns of neurons in the central nervous system and spinal cord where periods of rapid spiking are followed by quiescent, silent, periods. Bursting is thought to be important in the operation of robust central pattern...

  • Signals (biology)
  • Single-unit recording
    Single-unit recording
    In neurophysiology and neurology, single-unit recording is the use of an electrode to record the electrophysiological activity from a single neuron.-History:...

  • Central pattern generator
    Central pattern generator
    Central pattern generators are neural networks that produce rhythmic patterned outputs without sensory feedback. CPGs have been shown to produce rhythmic outputs resembling normal "rhythmic motor pattern production" even in isolation from motor and sensory feedback from limbs and other muscle...


External links


Animations