An
action potential (or
nerve impulse) is a transient alteration of the
transmembrane voltageMembrane potential is the voltage difference between the interior and exterior of a cell...
(or
membrane potential) across an
excitable membraneAn excitable membrane is a semipermeable membrane whose ionic conductances or, equivalently, ionic permeabilities are sensitive to the voltage across the membrane...
generated by the activity of
voltage-gated ion channelVoltage-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 the membrane. Action potentials play multiple roles in several types of excitable
cellsThe cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of an organism that is classified as living, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos...
such as neurons, myocytes, and electrocytes. The best known action potentials are pulse-like waves of
voltageVoltage is commonly used as a short name for electrical potential difference. Its corresponding SI unit is the volt...
that travel along axons of neurons.
A typical action potential is initiated at the
axon hillockThe axon hillock is the anatomical part of a neuron that connects the cell body to the axon.It is the location where the summation of inhibitory postsynaptic potentials and excitatory postsynaptic potentials from numerous synaptic inputs on the dendrites or cell body occurs.It is...
when the membrane is
depolarizedIn 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...
sufficiently (i.e. when its voltage is increased sufficiently). As the membrane potential is increased, sodium ion channels open, allowing the entry of
sodiumSodium is a metallic element with a symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals within "group 1"...
ions into the cell. This is followed by the opening of
potassium ion channelsIn 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
potassiumPotassium is the chemical element with the symbol K , atomic number 19, and atomic mass 39.0983. Potassium was first isolated from potash...
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 potentialRelatively static membrane potential of quiescent cells is called resting membrane potential , as opposed to the specific dynamic electrochemical phenomenona 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
hyperpolarizesHyperpolarization has several meanings:* Hyperpolarization occurs when the strength of the electric field across the width of a cell membrane increases...
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 feedbackPositive feedback, sometimes referred to as "cumulative causation", refers to a situation where some effect causes more of itself. A system undergoing positive feedback is unstable, that is, it will tend to spiral out of control as the effect amplifies itself....
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 largely determined by the properties of the excitable membrane and not the amplitude or duration of the stimulus. This all-or-nothing property of action potential sets it apart from graded potentials such as
receptor potentialReceptor 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 potentialIn 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,
synaptic potentialSynaptic potential is a phenomenon in neurobiology, regarding the electric potential in a synapse. It normally considers the postsynaptic potential, but can also regard the presynaptic potential, e.g...
s, which do 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 continual action of the sodium–potassium pump, which, with other ion transporters, maintains the normal ratio of ion concentrations across the membrane.
CalciumCalcium 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 grey alkaline earth metal, and is the fifth most abundant element by mass in the Earth's crust...
cations and
chlorideThe chloride ion is formed when the element chlorine picks up one electron to form an anion Cl
−...
anions are involved in a few types of action potentials, such as the
cardiac action potentialThe cardiac action potential is a specialized action potential in the heart, with unique properties necessary for function of the electrical conduction system of the heart.The cardiac action potential differs significantly in different portions of the heart...
and the action potential in the single-celled
algaAlgae are a large and diverse group of simple, typically autotrophic organisms, ranging from unicellular to multicellular forms. The largest and most complex marine forms are called seaweeds. They are photosynthetic, like plants, and "simple" because they lack the many distinct organs found in...
AcetabulariaAcetabularia is a genus of green algae, specifically of the Polyphysaceae family, Typically found in subtropical waters, Acetabularia is a single-cell 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 potentialIn 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 potentialIn 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 RanvierNodes 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 conductionSaltatory 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 terminalAxon 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 generally triggers the release of
neurotransmitterNeurotransmitters are endogenous chemicals which relay, amplify, and modulate signals between a neuron and another cell. Neurotransmitters are packaged into synaptic vesicles that cluster beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they...
into the synaptic cleft. Additionally, backpropagating action potentials have been recorded in the dendrites of
pyramidal neuronsPyramidal 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.
Ions and the forces driving their motion
Electrical signals within biological organisms are generally driven by
ionAn ion is an atom or molecule where the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge...
s. The most important cations for the action potential are
sodiumSodium is a metallic element with a symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals within "group 1"...
(Na
+) and
potassiumPotassium is the chemical element with the symbol K , atomic number 19, and atomic mass 39.0983. Potassium was first isolated from potash...
(K
+). Both of these are
monovalent cations that carry a single positive charge. Action potentials can also involve
calciumCalcium 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 grey alkaline earth metal, and is the fifth most abundant element by mass in the Earth's crust...
(Ca
2+), which is a
divalent cation that carries a double positive charge. The
chlorideThe chloride ion is formed when the element chlorine picks up one electron to form an anion Cl
−...
anion (Cl
−) plays a major role in the action potentials of some
algaeAlgae are a large and diverse group of simple, typically autotrophic organisms, ranging from unicellular to multicellular forms. The largest and most complex marine forms are called seaweeds. They are photosynthetic, like plants, and "simple" because they lack the many distinct organs found in...
, but plays a negligible role in the action potentials of most animals.
Ions cross the cell membrane under two influences:
diffusionMolecular diffusion, often called simply diffusion, is a net transport of molecules from a region of higher concentration to one of lower concentration by random molecular motion. The result of diffusion is a gradual mixing of material...
and
electric fieldIn physics, the space surrounding an electric charge or in the presence of a time-varying magnetic field has a property called an electric field. This electric field exerts a force on other electrically charged objects...
s. Let's start off with a simple example whereby two solutions are separated by a porous barrier. Let us further call these two solutions A and B. In this case, diffusion will ensure that they will eventually mix into equal solutions. This mixing occurs because of the difference in their concentrations. The region with high concentration will diffuse out towards the region with low concentration. To further the example, let solution A have 30 sodium ions and 30 chloride ions. Also, let solution B have only 20 sodium ions and 20 chloride ions. Assuming the barrier allows both types of ions to travel through it, then a steady state will be reached whereby both solutions have 25 sodium ions and 25 chloride ions. If, however, the porous barrier is selective to which ions are let through, then diffusion alone will not determine the resulting solution. Returning to the previous example, lets now construct a barrier that is only permeable to sodium ions. Since solution B has a lower concentration of both sodium and chloride, it will attract both ions from solution A. However, only sodium will travel through the barrier. This will result in an accumulation of sodium in solution B. Since sodium has a positive charge, this accumulation will make solution B more positive relative to solution A. Positive sodium ions will be less likely to travel to the now more positive B solution. This constitutes the second factor controlling ion flow, namely electric fields. The point at which this electric field completely counteracts the force due to diffusion is called the equilibrium potential. At this point, the net flow of this specific ion (in this case sodium) is zero.
Cell membrane
Each neuron is encased in a
cell membraneThe cell membrane is the biological membrane separating the interior of a cell from the outside environment....
. This membrane is nearly impermeable to
ionAn ion is an atom or molecule where the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge...
s. To transfer ions into and out of the neuron, the membrane provides two structures. Ion pumps use the cell's energy to continuously move ions in and out. They create concentration differences (between the inside and outside of the neuron) by transporting ions against their concentration gradients (from regions of low concentration to regions of high concentration). The ion channels then use this concentration difference to transport ions down their concentration gradients (from regions of high concentration to regions of low concentration). However, unlike the continuous transport by the ion pumps, the transport by the ion channels is non continuous. They only open and close in response to signals from their environment. This transport of ions through the ion channels then changes the voltage of the cell membrane. These changes are what bring about an action potential. As an analogy, ion pumps play the role of the battery that allows a radio circuit (the ion channels) to transmit a signal (action potential).
Membrane potential
The cell membrane acts as a barrier which prevents the inside solution (intracellular fluid) from mixing with the outside solution (extracellular fluid). These two solutions have different concentrations of their ions. Furthermore, this difference in concentrations leads to a difference in charge of the solutions. This creates a situation whereby one solution is more positive than the other. Therefore, positive ions will tend to gravitate towards the negative solution. Likewise, negative ions will tend to gravitate towards the positive solution. To quantify this property, one would like to somehow capture this relative positivity (or negativity). To do this, the outside solution is set as the zero voltage. Then the difference between the inside voltage and the zero voltage is determined. For example, if the outside voltage is 100 mV, and the inside voltage is 30 mV, then the difference is 70 mV. This difference is what is commonly referred to as the
membrane potentialMembrane potential is the voltage difference between the interior and exterior of a cell...
.
Ion channels
Ion channelIon channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of all living cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
s are
integral membrane proteinAn Integral Membrane Protein is a protein molecule that is permanently attached to the biological membrane...
s with a pore through which ions can travel between extracellular space and cell interior. Most channels are specific (selective) for one ion; for example, most potassium channels are characterized by 1000:1 selectivity ratio for potassium over sodium, though potassium and sodium ions have the same charge and differ only slightly in their radius. The channel pore is typically so small that ions must pass through it in single-file order.* Channel pore can be either open or closed for ion passage, although a number of channels demonstrate various sub-conductance levels. When a channel is open, ions permeate through the channel pore down the transmembrane concentration gradient for that particular ion. Rate of ionic flow through the channel, i.e. single-channel current amplitude, is determined by the maximum channel conductance and electrochemical driving force for that ion, which is the difference between instantaneous value of the membrane potential and the value of the
reversal potentialIn a biological membrane, the reversal potential of an ion is the membrane potential at which there is no net flow of ions from one side of the membrane to the other...
.
The action potential is a manifestation of different ion channels opening and closing at different times.
A channel may have several different states (corresponding to different
conformationsProteins are an important class of biological macromolecules present in all biological organisms, made up of such elements as carbon, hydrogen, nitrogen, oxygen, and sulphur. All proteins are polymers of amino acids. According to their physical size, proteins are nanoparticles...
of the protein), but each such state is either open or closed. In general, closed states correspond either to a contraction of the pore—making it impassable to the ion—or to a separate part of the protein stoppering the pore. For example, the voltage-dependent sodium channel undergoes
inactivation, in which a portion of the protein swings into the pore, sealing it. This inactivation shuts off the sodium current and plays a critical role in the action potential.
Ion channels can be classified by how they respond to their environment. For example, the ion channels involved in the action potential are
voltage-sensitive channels; they open and close in response to the voltage across the membrane.
Ligand-gated channels form another important class; these ion channels open and close in response to the binding of a
ligand moleculeIn biochemistry and pharmacology, a ligand is a substance that is able to bind to and form a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as...
, such as a
neurotransmitterNeurotransmitters are endogenous chemicals which relay, amplify, and modulate signals between a neuron and another cell. Neurotransmitters are packaged into synaptic vesicles that cluster beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they...
. Other ion channels open and close with mechanical forces. Still other ion channels—such as those of sensory neurons—open and close in response to other stimuli, such as light, temperature or pressure.
Ion pumps
The ionic currents of the action potential flow in response to
concentrationIn chemistry, concentration is the measure of how much of a given substance there is mixed with another substance. This can apply to any sort of chemical mixture, but most frequently the concept is limited to homogeneous solutions, where it refers to the amount of solute in the solvent.To...
differences of the ions across the
cell membraneThe cell membrane is the biological membrane separating the interior of a cell from the outside environment....
. These concentration differences are established by ion pumps, which are
integral membrane proteinAn Integral Membrane Protein is a protein molecule that is permanently attached to the biological membrane...
s that carry out
active transportActive transport is the mediated process of moving particles across a biological membrane against a concentration gradient. If the process uses chemical energy, such as from adenosine triphosphate , it is termed primary active transport. Secondary active transport involves the use of an...
, i.e., use cellular energy (ATP) to "pump" the ions against their concentration gradient. Such ion pumps take in ions from one side of the membrane (decreasing its concentration there) and release them on the other side (increasing 'its concentration there). The ion pump most relevant to the action potential is the
sodium–potassium pumpNa+/K+-ATPase is an enzyme located in the plasma membrane in all animals.- Sodium-Potassium pumps :Active transport is responsible for the well-established observation that cells...
, which transports three sodium ions out of the cell and two potassium ions in. Consequently, the concentration of
potassiumPotassium is the chemical element with the symbol K , atomic number 19, and atomic mass 39.0983. Potassium was first isolated from potash...
ions K
+ inside the neuron is roughly 20-fold larger than the outside concentration, whereas the sodium concentration outside is roughly ninefold larger than inside. Similarly, other ions have different concentrations inside and outside the neuron, such as
calciumCalcium 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 grey alkaline earth metal, and is the fifth most abundant element by mass in the Earth's crust...
,
chlorideThe chloride ion is formed when the element chlorine picks up one electron to form an anion Cl
−...
and
magnesiumMagnesium is a chemical element with the symbol Mg, atomic number 12 and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the earth's crust by mass, although ninth in the Universe as a whole...
.
Ion pumps influence the action potential only by establishing the relative ratio of intracellular and extracellular ion concentrations. The action potential mainly involves the opening and closing of ion channels, not ion pumps. If the ion pumps are turned off by removing their energy source, or by adding an inhibitor such as
ouabainOuabain is the familiar name of g-strophanthin, a poisonous cardiac glycoside.-Sources:...
, the axon can still fire hundreds of thousands of action potentials before their amplitudes begin to decay significantly. In particular, ion pumps play no significant role in the repolarization of the membrane after an action potential.
Resting potential
As described in the section Ions and the forces driving their motion, equilibrium or reversal potential of an ion is the value of transmembrane voltage at which the electric force generated by diffusional movement of the ion down its concentration gradient becomes equal to the molecular force of that diffusion. The equilibrium potential for any ion can be calculated using the
Nernst equationIn electrochemistry, the Nernst equation is an equation which 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 example, reversal potential for potassium ions will be as follows
where
- Eeq,K+ is the equilibrium potential for potassium, measured in volt
The volt is the SI derived unit of electromotive force, commonly called "voltage". It is also the unit for the related but slightly different quantity electric potential difference...
s
- R is the universal gas constant
The gas constant is a physical constant which is featured in a large number of fundamental equations in the physical sciences, such as the ideal gas law and the Nernst equation...
, equal to 8.314 jouleThe joule , named for James Prescott Joule, is the derived unit of energy in the International System of Units. It is the energy exerted by a force of one newton acting to move an object through a distance of one metre...
s·K-1·mol-1
- T is the absolute temperature, measured in kelvin
The kelvin is a unit increment of temperature and is one of the seven SI base units. The Kelvin scale is a thermodynamic temperature scale where absolute zero, the theoretical absence of all thermal energy, is zero kelvin...
s (= K = degrees Celsius + 273.15)
- z is the number of elementary charge
The elementary charge, usually denoted e, is the electric charge carried by a single proton, or equivalently, the negative of the electric charge carried by a single electron. This is a fundamental physical constant. To avoid confusion over its sign, e is sometimes called the "elementary positive...
s of the ion in question involved in the reaction
- F is the Faraday constant
In physics and chemistry, the Faraday constant is the magnitude of electric charge per mole of electrons. While most uses of the Faraday constant, denoted F, have been replaced by the standard SI unit, the coulomb, the Faraday is still widely used in calculations in electrochemistry...
, equal to 96,485 coulombThe coulomb is the SI derived unit of electric charge. It is named after Charles-Augustin de Coulomb.- Definition :If 2 like point charges of equal magnitudes are placed in a vacuum at a distance of 1 metre away from each other and if they repel each other with a force of 9*1000000000 Newton, then...
s·mol-1 or J·V-1·mol-1
- [K+]o is the extracellular concentration of potassium, measured in mol
The mole is a unit of amount of substance: it is an SI base unit, and one of the few units used to measure this physical quantity. The name "mole" was coined in German by Wilhelm Ostwald in 1893, although the related concept of equivalent mass had been in use at least a century earlier...
·m-3 or mmol·l-1
- [K+]i is the intracellular concentration of potassium
Even if two different ions have the same charge (ie. K
+ and Na
+), they can still have very different equilibrium potentials, provided their outside and/or inside concentrations differ. Take, for example, the equilibrium potentials of potassium and sodium in neurons. The potassium equilibrium potential
EK is -84 mV with 5 mM potassium outside and 140 mM inside. The sodium equilibrium potential, on the other hand,
ENa is approximately +40mV with 1-2 mM sodium inside and 120 mM outside.
[Membrane potentials are defined relative to the exterior of the cell; thus, a potential of −70 mV implies that the interior of the cell is negative relative to the exterior.]
However, there is an equilibrium membrane potential
Em at which the
net flow of all ions across the membrane is zero. This potential is calculated by the
Goldman equationThe 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...
It is essentially the Nernst equation, in that it is based on the charges of the ions in question, as well as the difference between their inside and outside concentrations. However, it also takes into consideration the relative permeability of the plasma membrane to each ion in question.
for the three monovalent ions most important to action potentials: potassium (K
+), sodium (Na
+), and chloride (Cl
−). Being an anion, the chloride terms are treated differently than the cation terms; the inside concentration is in the numerator, and the outside concentration is in the denominator, which is reversed from the cation terms.
Pi stands for the
permeabilityPermeability, permeable and semipermeable have several meanings:*Permeability , the degree of magnetization of a material in response to a magnetic field...
of the ion type i. If calcium ions are also considered, which are critically important for action potentials in muscles, the formula for the equilibrium potential becomes more complicated.
Generation of resting membrane potential is explicitly explained by the Goldman equation. The resting plasma membrane of most animal cells is much more permeable to K
+, which results in the resting potential
Vrest to be close to the potassium equilibrium potential.
It is important to realize, that ionic and water permeability of a pure lipid bilayer is very small, and it is similarly negligible for ions of comparable size, such as Na
+ and K
+. The cell membranes, however, contain a large number of
ion channelIon channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of all living cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
s, water channels (
aquaporinAquaporins are proteins embedded in the cell membrane that regulate the flow of water. They are "the plumbing system for cells."Aquaporins are integral membrane proteins from a larger family of major intrinsic proteins that form pores in the membrane of biological cells.Genetic defects involving...
s), and various ionic pumps, exchangers, and transporters, which dramatically and selectively increase permeability of the membrane for different ions. The relatively high membrane permeability for potassium ions at resting potential results from
Inward-rectifier potassium ion channelInwardly rectifying potassium channels are a specific subset of potassium selective ion channels. To date, seven subfamilies have been identified in various mammalian cell types...
s which are open at negative voltages, and so called leak potassium conductances such as open rectifier K
+ channel (ORK
+) which are locked in open state. These potassium channels should not be confused with voltage-activated K
+ channels responsible for membrane repolarization during action potential.
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 potentialThe cardiac action potential is a specialized action potential in the heart, with unique properties necessary for function of the electrical conduction system of the heart.The cardiac action potential differs significantly in different portions of the heart...
). However, the main excitable cell is the
neuronA neuron is an excitable cell in the nervous system that processes and transmits information by electrochemical signaling. Neurons are the core components of the brain, the vertebrate spinal cord, the invertebrate ventral nerve cord, and the peripheral nerves...
, which also has the simplest mechanism for the action potential.
Neurons are electrically excitable cells generally comprised of one or more
dendriteDendrites 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
synapsesChemical 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 buttons. 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
somaThe soma , or cyton or perikaryon , is the bulbous end of a neuron, containing the cell nucleus. The word soma is Greek, meaning "body"; the soma of a neuron is often called the "cell body"...
. The soma houses the
nucleusIn cell biology, the nucleus , also sometimes referred to as the "control center", 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...
, 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 hillockThe axon hillock is the anatomical part of a neuron that connects the cell body to the axon.It is the location where the summation of inhibitory postsynaptic potentials and excitatory postsynaptic potentials from numerous synaptic inputs on the dendrites or cell body occurs.It is...
. This region is characterized by having an incredibly high concentration of voltage activated sodium channels. It is generally 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
axonAn axon or nerve fiber is a long, slender projectionof a nerve cell, or neuron, that conducts electrical impulsesaway 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
myelinMyelin 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...
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 both 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 ranvierNodes 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
axonAn axon or nerve fiber is a long, slender projectionof a nerve cell, or neuron, that conducts electrical impulsesaway 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 hillockThe axon hillock is the anatomical part of a neuron that connects the cell body to the axon.It is the location where the summation of inhibitory postsynaptic potentials and excitatory postsynaptic potentials from numerous synaptic inputs on the dendrites or cell body occurs.It is...
. 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.
Neurotransmission
Action potentials are most commonly initiated by
excitatory postsynaptic potentialIn 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,
neurotransmitterNeurotransmitters are endogenous chemicals which relay, amplify, and modulate signals between a neuron and another cell. Neurotransmitters are packaged into synaptic vesicles that cluster beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they...
molecules are released by the presynaptic
neuronA neuron is an excitable cell in the nervous system that processes and transmits information by electrochemical signaling. Neurons are the core components of the brain, the vertebrate spinal cord, the invertebrate ventral nerve cord, and the peripheral nerves...
. These neurotransmitters then bind to receptors on the postsynaptic cell. This binding opens various types of
ion channelIon channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of all living 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 membraneThe cell membrane is the biological membrane separating the interior of a cell from the outside environment....
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 hillockThe axon hillock is the anatomical part of a neuron that connects the cell body to the axon.It is the location where the summation of inhibitory postsynaptic potentials and excitatory postsynaptic potentials from numerous synaptic inputs on the dendrites or cell body occurs.It is...
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 counter-acting
inhibitory postsynaptic potentialAn 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 synapseAn electrical synapse is a mechanical and electrically conductive link between two abutting neuron cells that is formed at a narrow gap between the pre- and postsynaptic cells known as a gap junction...
s. Due to the direct connection between excitable cells in the form of
gap junctionA 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. The free flow of ions between cells enables rapid non-chemical mediated transmission. Rectifying channels ensure that action potentials only move in one direction through an electrical synapse. In the human nervous system this type of synapse is uncommon however.
"All-or-none" principle
The
amplitudeAmplitude is the magnitude of change in the oscillating variable, with each oscillation, within an oscillating system. For instance, sound waves 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 which produced it. In other words, larger currents do not create larger action potentials. Therefore action potentials are said to be
all-or-none, since they either occur fully or they do not occur at all. Instead, the
frequencyFrequency 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 potentialReceptor 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 neuronAn olfactory receptor neuron, also called an olfactory sensory neuron, is the primary transduction cell in the olfactory system.-In vertebrates:...
and
Meissner's corpuscleMeissner's corpuscles are a type of mechanoreceptor. They are a type of nerve endings in the skin that are 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
smellOlfaction refers to 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
touchThe somatosensory system is a diverse sensory system comprising 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
neurotransmitterNeurotransmitters are endogenous chemicals which relay, amplify, and modulate signals between a neuron and another cell. Neurotransmitters are packaged into synaptic vesicles that cluster beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they...
, or into continuous
graded potentialsReceptor 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
earThe ear is the organ that detects sound. The vertebrate ear shows a common biology from fish to humans, with variations in structure according to order and species. It not only acts as a receiver for sound, but plays a major role in the sense of balance and body position...
,
hair cellHair 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 channelsStretch-activated or stretch-gated ion channels are ion channels which open their pores in response to mechanical deformation of a neuron's plasma membrane.-Mechanism:...
, which may cause
neurotransmitterNeurotransmitters are endogenous chemicals which relay, amplify, and modulate signals between a neuron and another cell. Neurotransmitters are packaged into synaptic vesicles that cluster beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they...
molecules to be released. Similarly, in the human
retinaThe 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 cellAs 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
amacrine cellAmacrine 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) do not produce action potentials; only the third layer, the
ganglion cellA 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 nerveThe optic nerve, also called cranial nerve II, transmits visual information from the retina to the brain.-Anatomy:The optic nerve is the second of twelve paired cranial nerves but is considered to be part of the central nervous system as it is derived from an outpouching of the diencephalon during...
.
Pacemaker potentials
In the cases of neurotransmission and 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 potentialIn 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 pacemakerThe contractions of the heart are controlled by chemical impulses. The rate these impulses fire controls the heart rate.The cells that create these rhythmical impulses are called pacemaker cells, and they directly control the heart rate...
cells of the
sinoatrial nodeThe sinoatrial node is the impulse-generating tissue located in the right atrium of the heart, and thus the generator of 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
heartThe heart is a muscular organ found in all vertebrates 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 rateHeart rate is determined by the number of heartbeats per unit of time, typically expressed as beats per minute , it can vary with as the body's need for oxygen changes, such as during exercise or sleep. The measurement of heart rate is used by medical professionals to assist in the diagnosis and...
can be altered by pharmaceuticals as well as signals from the
sympatheticThe Sympathetic Nervous System is a branch of the autonomic nervous system along with the enteric nervous system and parasympathetic nervous system. It is always active at a basal level and becomes more active during times of stress...
and
parasympatheticThe parasympathetic nervous system is a division of the autonomic nervous system , along with the sympathetic nervous system and enteric nervous system . The ANS is a subdivision of the peripheral nervous system . ANS sends fibers to three tissues: cardiac muscle, smooth muscle, or glandular tissue...
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
burstingBursting is a rapid signaling mode in neurons whereby clusters of two or more action potentials are emitted as a single signaling event. A burst of two spikes is called a doublet, three spikes - triplet, four - quadruplet, etc...
.
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 finally the refractory period. During the rising phase the membrane potential depolarises (becomes more positive). The point at which depolarisation 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 hyperpolarises (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 voltageMembrane potential is the voltage difference between the interior and exterior of a cell...
Vm. This changes the membrane's permeability to those ions. Secondly, according to the
Goldman equationThe 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 feedbackPositive feedback, sometimes referred to as "cumulative causation", refers to a situation where some effect causes more of itself. A system undergoing positive feedback is unstable, that is, it will tend to spiral out of control as the effect amplifies itself....
, 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 HodgkinSir Alan Lloyd Hodgkin, OM, KBE, FRS was a British physiologist and biophysicist, who won the 1963 Nobel Prize in Physiology or Medicine.-Early life:...
and
Andrew HuxleySir Andrew Fielding Huxley, OM, FRS is an English physiologist and biophysicist, who won the 1963 Nobel Prize in Physiology or Medicine for his work with Alan Lloyd Hodgkin on the basis of nerve action potentials, the electrical impulses that enable the activity of an organism to be coordinated by...
in 1952, for which they were awarded the
Nobel Prize in Physiology or MedicineThe Nobel Prize in Physiology or Medicine is awarded once a year by the Swedish Karolinska Institute. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in Physics, Chemistry, Literature, Peace, and Physiology or Medicine...
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 hillockThe axon hillock is the anatomical part of a neuron that connects the cell body to the axon.It is the location where the summation of inhibitory postsynaptic potentials and excitatory postsynaptic potentials from numerous synaptic inputs on the dendrites or cell body occurs.It is...
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 synapseChemical 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 neurons or
pacemaker potentialIn 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 initial membrane permeability to potassium is low, but much higher than that of other 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 feedbackPositive feedback, sometimes referred to as "cumulative causation", refers to a situation where some effect causes more of itself. A system undergoing positive feedback is unstable, that is, it will tend to spiral out of control as the effect amplifies itself....
) 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 provoke 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, driving the membrane voltage back down. 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.
Hyperpolarization ("undershoot")
The raised voltage opened many more potassium channels than usual, and these do not close right away when the membrane returns to its normal resting voltage. 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, a
hyperpolarization 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 HodgkinSir Alan Lloyd Hodgkin, OM, KBE, FRS was a British physiologist and biophysicist, who won the 1963 Nobel Prize in Physiology or Medicine.-Early life:...
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,
[Stevens, pp. 21–23.] 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
The evolutionary need for the fast and efficient transduction of electrical signals in nervous system resulted in appearance of
myelinMyelin 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...
sheaths around neuronal axons. Myelin is a multilamellar membrane which enwraps the axon in segments separated by intervals known as
nodes of RanvierNodes 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 cellNamed after the German physiologist Theodor Schwann, Schwann cells are a variety of glial cell that keep peripheral nerve fibres alive. In myelinated axons, Schwann cells form the myelin sheath . The sheath is not continuous. Individual myelinating Schwann cells cover about 100 micrometre of an...
s exclusively in the
peripheral nervous systemThe peripheral nervous system resides or extends outside the central nervous system , which consists of the brain and spinal cord. The main function of the PNS is to connect the CNS to the limbs and organs. Unlike the central nervous system, the PNS is not protected by bone or by the blood-brain...
, and by
oligodendrocyteOligodendrocytes , or oligodendroglia , are a variety of neuroglia. Their main function is the insulation of the axons exclusively in the central nervous system of the higher vertebrates, a function performed by Schwann cells in the peripheral nervous system...
s exclusively in the
central nervous systemThe central nervous system is the part of the nervous system that functions to coordinate the activity of all parts of the bodies of bilaterian animals—that is, all animals more advanced than sponges or jellyfish. In vertebrates, the central nervous system is enclosed in the meninges. It contains...
. 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
vertebrateVertebrates are members of the subphylum Vertebrata, chordates with backbones or spinal columns. About 58,000 species of vertebrates have been described. Vertebrata is the largest subphylum of chordates, and contains many familiar groups of large land animals. Vertebrates comprise cyclostomes, bony...
s, but an analogous system has been discovered in a few invertebrates, such as some species of
shrimpShrimp 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 generally 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 next 1 or 2 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 conductionSaltatory 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 TasakiDr. Ichiji Tasaki was a Japanese biophysicist and physician involved in research relating to the electical impulses in the nervous system. He is crediting with discovering the insulating function of the myelin sheath...
and Taiji Takeuchi*
* and from
Andrew HuxleySir Andrew Fielding Huxley, OM, FRS is an English physiologist and biophysicist, who won the 1963 Nobel Prize in Physiology or Medicine for his work with Alan Lloyd Hodgkin on the basis of nerve action potentials, the electrical impulses that enable the activity of an organism to be coordinated by...
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
micrometreA micrometre or micron is one millionth of a metre,or equivalently one thousandth of a millimetre....
), 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 advantageNatural selection is the process by which heritable traits that make it more likely for an organism to survive and successfully reproduce become more common in a population over successive generations...
, 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 sclerosisMultiple sclerosis is an idiopathic disease of suspected autoimmune cause, in which the body's immune response attacks a person's central nervous system , leading to demyelination. Disease onset usually occurs in young adults, and it is more common in females...
, in which the breakdown of myelin impairs coordinated movement.
Cable theory
The flow of currents within an axon can be described quantitatively by
cable theoryClassical 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 KelvinWilliam Thomson, 1st Baron Kelvin , OM, GCVO, PC, PRS, FRSE, was a British mathematical physicist and engineer...
to model the transatlantic telegraph cable and was shown to be relevant to neurons by
HodgkinSir Alan Lloyd Hodgkin, OM, KBE, FRS was a British physiologist and biophysicist, who won the 1963 Nobel Prize in Physiology or Medicine.-Early life:...
and
RushtonWilliam 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 equationIn mathematics, partial differential equations are a type of differential equation, i.e., a relation involving an unknown function of several independent variables and its 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=CVIn electromagnetism and electronics, capacitance is the ability of a body to hold an electrical charge.Capacitance is also a measure of the amount of electric charge stored for a given electric potential. A common form of charge storage device is a parallel-plate capacitor...
); as the resistance increases, less charge is transferred per unit time, making the equilibration slower. Similarly, 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
Action potentials that reach the synaptic knobs generally cause a
neurotransmitterNeurotransmitters are endogenous chemicals which relay, amplify, and modulate signals between a neuron and another cell. Neurotransmitters are packaged into synaptic vesicles that cluster beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they...
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
vesiclesIn 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 contentsExocytosis 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
neurotoxinA 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
tetanospasminTetanospasmin is the neurotoxin produced by the vegetative spore 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 sometimes called spasmogenic toxin, tetanus toxin or...
and
botulinum toxinBotulinum toxin is a medication and a neurotoxic protein produced by the bacterium Clostridium botulinum, and is held to be the most toxic substance known to mankind with an LD50 of roughly 0.005-0.05 µg/kg...
, which are responsible for
tetanusTetanus, also called lockjaw, 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, obligate anaerobic bacterium Clostridium tetani. Infection generally occurs through...
and
botulismBotulism also known as botulinus intoxication is a rare but serious paralytic illness caused by botulinum toxin, which is produced by the bacterium Clostridium botulinum...
, 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
connexinConnexins, 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
neurotransmitterNeurotransmitters are endogenous chemicals which relay, amplify, and modulate signals between a neuron and another cell. Neurotransmitters are packaged into synaptic vesicles that cluster beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they...
s across the synaptic cleft. Hence, electrical synapses are used whenever fast response and coordination of timing are crucial, as in
escape reflexEscape 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
retinaThe 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
vertebrateVertebrates are members of the subphylum Vertebrata, chordates with backbones or spinal columns. About 58,000 species of vertebrates have been described. Vertebrata is the largest subphylum of chordates, and contains many familiar groups of large land animals. Vertebrates comprise cyclostomes, bony...
s, and the
heartThe heart is a muscular organ found in all vertebrates 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 junctionA neuromuscular junction is the synapse or junction of the axon terminal of a motoneuron 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
axonAn axon or nerve fiber is a long, slender projectionof a nerve cell, or neuron, that conducts electrical impulsesaway from the neuron's cell body or soma....
of a
motor neuronIn 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
acetylcholineThe chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans. Acetylcholine is one of many neurotransmitters in the autonomic nervous system and the only neurotransmitter used in the motor division...
, which binds to the acetylcholine receptor, an integral membrane protein in the membrane (the
sarcolemmaThe 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
hydrolyzedHydrolysis is a chemical reaction during which one or more water molecules are split into hydrogen and hydroxide ions, which may go on to participate in further reactions. It is the type of reaction that is used to break down certain polymers, especially those made by step-growth polymerization...
by the enzyme,
acetylcholinesteraseAcetylcholinesterase, also known as AChE, is an enzyme that degrades the neurotransmitter acetylcholine, producing choline and an acetate group. It is mainly found at neuromuscular junctions and cholinergic synapses in the central nervous system, where its activity serves to terminate synaptic...
, 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 agentNerve agents, also referred to as nerve gases though these chemicals are liquid at room temperature, are a class of phosphorus-containing organic chemicals that disrupt the mechanism by which nerves transfer messages to organs...
s
sarinSarin, also known by its NATO designation of GB, is an extremely toxic substance whose sole application is as a nerve agent. As a chemical weapon, it is classified as a weapon of mass destruction by the United Nations in UN Resolution 687...
and
tabunTabun may refer to:* Tabun Cave, a cave near Tabun, Israel where remains of Neanderthal Man were found.* A tabun oven, a clay oven used to make tabun bread...
, and the insecticides
diazinonDiazinon , a colorless to dark brown liquid, is a thiophosphoric acid ester developed in 1952 by Ciba-Geigy, a Swiss chemical company . It is a nonsystemic organophosphate insecticide formerly used to control cockroaches, silverfish, ants, and fleas in residential, non-food buildings...
and
malathionMalathion is an organophosphate parasympathomimetic which binds irreversibly to cholinesterase. Malathion is an insecticide of relatively low human toxicity....
.
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
calciumCalcium 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 grey 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 nodeThe sinoatrial node is the impulse-generating tissue located in the right atrium of the heart, and thus the generator of 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 potentialIn 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 nodeThe atrioventricular node is a part of electrical control system of the heart that co-ordinates heart rate. It electrically connects atrial and ventricular chambers...
(AV node), which is normally the only conduction pathway between the atria and the
ventriclesIn the heart, a ventricle is a heart chamber which collects blood from an atrium and pumps it out of the heart...
. Action potentials from the AV node travel through the
bundle of HisThe bundle of His, also 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]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 neuronA neuron is an excitable cell in the nervous system that processes and transmits information by electrochemical signaling. Neurons are the core components of the brain, the vertebrate spinal cord, the invertebrate ventral nerve cord, and the peripheral nerves...
s found in the cerebellumThe cerebellum is a region of the brain that plays an important role in the integration of sensory perception, coordination and motor control...
. 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
quinidineQuinidine 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:...
,
lidocaineLidocaine 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, and in minor surgery....
,
beta blockerBeta blockers is a class of drugs used for various indications, but particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction , and hypertension. Propranolol was the first clinically useful beta adrenergic receptor antagonist. Invented by Sir James W...
s, and
verapamilVerapamil 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
sarcolemmaThe 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
calciumCalcium 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 grey alkaline earth metal, and is the fifth most abundant element by mass in the Earth's crust...
ions that free up the
tropomyosinTropomyosin 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 junctionA neuromuscular junction is the synapse or junction of the axon terminal of a motoneuron 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
neurotoxinA 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 pudicaMimosa 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 within minutes...
), arose independently from that in metazoan excitable cells.
Taxonomic distribution and evolutionary advantages
Action potentials are found throughout
multicellular organismMulticellular organisms are organisms consisting of more than one cell, and having differentiated cells that perform specialized functions in the organism...
s, including
plantPlants are living organisms belonging to the kingdom Plantae. They include familiar organisms such as trees, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The scientific study of plants, known as botany, has identified about 350,000 extant species of plants, defined as seed plants,...
s,
invertebrateAn invertebrate is an animal without a vertebral column. The group includes 95% of all animal species — all animals except those in the Chordate subphylum Vertebrata ....
s such as
insectInsects are arthropods, having a hard exoskeleton, a three-part body , three pairs of jointed legs, compound eyes, and two antennae. They are the most diverse group of animals on the planet and include more than a million species that are already described. Insects represent more than half of all...
s, and
vertebrateVertebrates are members of the subphylum Vertebrata, chordates with backbones or spinal columns. About 58,000 species of vertebrates have been described. Vertebrata is the largest subphylum of chordates, and contains many familiar groups of large land animals. Vertebrates comprise cyclostomes, bony...
s such as
reptileReptiles, or members of the class Reptilia, are air-breathing, generally "cold-blooded" amniotes that generally have skin covered in scales or scutes. They are tetrapods and lay amniote eggs, whose embryos are surrounded by the amnion membrane...
s and
mammalMammals are a class of vertebrate animals whose females are characterized by the possession of mammary glands while both males and females are characterized by sweat glands, hair, three middle ear bones used in hearing, and a neocortex region in the brain.Mammals are divided into three main...
s. Sponges seem to be the main
phylumIn biology, a phylum ["Phylum" is adopted from the Greek phylai, the clan-based voting groups in Greek city-states.] is a taxonomic rank below Kingdom and above Class...
of multicellular
eukaryoteA eukaryote is an organism whose cells contain complex structures enclosed within membranes. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear envelope, within which the genetic material is carried...
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 soundSound is a vibration that travels through an elastic medium as a wave. The speed of sound describes how far this wave travels in a given amount of time. In dry air at , the speed of sound is . This equates to , or about one mile in five seconds...
. No material object could convey a signal that rapidly throughout the body; 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 generators can be defined as neural networks that can endogenously produce rhythmic patterned outputs" or as "neural circuits that generate periodic motor commands for rhythmic movements such as locomotion." CPGs have been shown to produce rhythmic outputs resembling normal...
s and mimicked in
artificial neural networkAn artificial neural network , usually called "neural network" , is a mathematical model or computational model that tries to simulate the structure and/or functional aspects of biological neural networks. It consists of an interconnected group of artificial neurons and processes information using...
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
electrodeAn 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
squidSquid are marine 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 and two longer tentacles arranged in pairs...
genus
LoligoLoligo is a genus of squids and one of the most representative and widely distributed group 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 clampThe voltage clamp is used by electrophysiologists to measure the ion currents across a neuronal membrane while holding the membrane voltage at a set level. Neuronal membranes 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 noiseElectronic noise is a random signal characteristic of all electronic circuits. Depending on the circuit, the noise generated by electronic devices can vary greatly. Noise can be produced by several different effects. Thermal noise and shot noise are inherent to all devices...
, the current
IC associated with the
capacitanceIn electromagnetism and electronics, capacitance is the ability of a body to hold an electrical charge.Capacitance is also a measure of the amount of electric charge stored for a given electric potential. A common form of charge 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 cageA 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 electrical fields....
s and electronics with high
input impedanceThe input impedance, load impedance, or external impedance of a circuit or electronic device is the Thévenin equivalent impedance looking into its input.-Audio systems:...
, 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
ÅThe ångström or angstrom is an internationally recognized unit of length equal to 0.1 nanometre or 1 metres. It is named after Anders Jonas Ångström...
(10
nmA nanometre is a unit of length in the metric system, equal to one billionth of a meter....
), which also confers high input impedance. Action potentials may also be recorded with small metal electrodes placed just next to a neuron, with
neurochipA 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
EOSFETAn 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 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 clampThe 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 NeherErwin 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 SakmannBert Sakmann is a German cell physiologist. He shared the Nobel Prize in Physiology or Medicine with Erwin Neher in 1991 for their work on "the function of single ion channels in cells," and invention of the patch clamp...
. For this they were awarded the
Nobel Prize in Physiology or MedicineThe Nobel Prize in Physiology or Medicine is awarded once a year by the Swedish Karolinska Institute. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in Physics, Chemistry, Literature, Peace, and Physiology or Medicine...
in 1991. Patch-clamping verified that ionic channels have discrete states of conductance, such as open, closed and inactivated.
Optical imagingOptical 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
neurotoxinA 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.
TetrodotoxinTetrodotoxin is a potent neurotoxin with no known antidote. There have been succesful tests of a possible antidote in mice, but further tests must be carried out to determine efficacy in humans...
from the
pufferfishTetraodontidae is a family of primarily marine and estuarine fish. The family includes many familiar species which are variously called puffers, balloonfish, blowfish, bubblefish, globefish, swellfish, toadfish, and toadies...
and
saxitoxinSaxitoxin 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
GonyaulaxGonyaulax is a genus of Alveolata.It includes the species Gonyaulax polyedra....
(the
dinoflagellateThe 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. About half of all dinoflagellates are photosynthetic, and these make up the...
genus responsible for "
red tideParalytic shellfish poisoning is one of the four recognized syndromes of shellfish poisoning . All four syndromes share some common features and are primarily associated with bivalve molluscs...
s") block action potentials by inhibiting the voltage-sensitive sodium channel;*
* similarly,
dendrotoxinDendrotoxins 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 mambaMambas, of the genus Dendroaspis, are fast-moving land-dwelling snakes of Africa. They belong to the family of Elapidae which includes cobras, coral snakes, kraits and, debatably, sea snakes although these are now classed as Hydrophiidae, all of which can be extremely deadly. The black mamba...
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 chromatographyAffinity chromatography is a method of separating biochemical mixtures, based on a highly specific biological interaction such as that between antigen and antibody, enzyme and substrate, or receptor and ligand...
or in assaying their concentration. However, such inhibitors also make effective neurotoxins, and have been considered for use as
chemical weaponChemical warfare involves using the toxic properties of chemical substances as weapons to kill, injure, or incapacitate an enemy....
s. Neurotoxins aimed at the ion channels of insects have been effective
insecticideAn 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
permethrinPermethrin 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
synapsesChemical 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 junctionA neuromuscular junction is the synapse or junction of the axon terminal of a motoneuron 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
frogFrogs are amphibians in the order Anura , formerly referred to as Salientia . Most frogs are characterized by long hind legs, a short body, webbed digits , protruding eyes and the absence of a tail...
s by
Luigi Galvani Luigi Galvani was an Italian physician and physicist who lived and died in Bologna. In 1771, he discovered that the muscles of dead frogs twitched when struck by a spark.ref> – Eric Weisstein’s World of Scientific Biolgraph. This was one of the first forays into the study of...
, who studied it from 1791 to 1797. Galvani's results stimulated
Alessandro VoltaCount Alessandro Giuseppe Antonio Anastasio Volta was an Italian physicist known especially for the development of the first electric cell in 1800.-Early life and works:...
to develop the
Voltaic pileA 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 batteryAn electrical battery is a combination of one or more electrochemical cells, used to convert stored chemical energy into electrical energy. Since the invention of the first Voltaic pile in 1800 by Alessandro Volta, the battery has become a common power source for many household and industrial...
—with which he studied animal electricity (such as
electric eelThe electric eel or temblador , is an electrical fish, and the only species of the genus Electrophorus. It is capable of generating powerful electric shocks, 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-currentDirect current is the undirectional 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 be through...
voltageVoltage is commonly used as a short name for electrical potential difference. Its corresponding SI unit is the volt...
s.
Scientists of the 19th century studied the propagation of electrical signals in whole
nerveA 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
neuronA neuron is an excitable cell in the nervous system that processes and transmits information by electrochemical signaling. Neurons are the core components of the brain, the vertebrate spinal cord, the invertebrate ventral nerve cord, and the peripheral nerves...
s) and demonstrated that nervous tissue was made up of
cellsThe cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of an organism that is classified as living, 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 MatteucciCarlo 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 membraneThe cell membrane is the biological membrane separating the interior of a cell from the outside environment....
s had a voltage across them and could produce
direct currentDirect current is the undirectional 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 be through...
. Matteucci's work inspired the German physiologist,
Emil du Bois-ReymondEmil 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 HelmholtzHermann 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 was made up of discrete cells, the Spanish physician
Santiago Ramón y CajalSantiago Ramón y Cajal was a Spanish histologist, physician, pathologist and Nobel laureate. His pioneering investigations of the microscopic structure of the brain were so original and influential that he is considered by many to be the greatest neuroscientist of all time...
and his students used a stain developed by
Camillo GolgiCamillo Golgi was an Italian physician, pathologist, scientist, and Nobel laureate.-Biography:Camillo Golgi was born in Corteno . 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 PhysiologyThe Nobel Prize in Physiology or Medicine is awarded once a year by the Swedish Karolinska Institute. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in Physics, Chemistry, Literature, Peace, and Physiology or Medicine...
. Their work resolved a long-standing controversy in the
neuroanatomyNeuroanatomy is the study of the anatomy of nervous tissue and neural structures of the nervous system. In vertebrate animals, the routes that the myriad nerves take from the brain to the rest of the body , and the internal structure of the brain in particular, are both extremely elaborate...
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 BernsteinJulius 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
permeabilityPermeability, permeable and semipermeable have several meanings:*Permeability , the degree of magnetization of a material in response to a magnetic field...
of the axonal membrane to ions.* Bernstein's hypothesis was confirmed by
Ken ColeKenneth 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 LapicqueLouis Lapicque is 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 systemsDynamics may refer to:In Physics:*Dynamics , in physics, dynamics refers to time evolution of physical processes...
of ionic conductances. In 1949,
Alan HodgkinSir Alan Lloyd Hodgkin, OM, KBE, FRS was a British physiologist and biophysicist, who won the 1963 Nobel Prize in Physiology or Medicine.-Early life:...
and
Bernard KatzSir 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 HuxleySir Andrew Fielding Huxley, OM, FRS is an English physiologist and biophysicist, who won the 1963 Nobel Prize in Physiology or Medicine for his work with Alan Lloyd Hodgkin on the basis of nerve action potentials, the electrical impulses that enable the activity of an organism to be coordinated by...
, in which they applied the
voltage clampThe voltage clamp is used by electrophysiologists to measure the ion currents across a neuronal membrane while holding the membrane voltage at a set level. Neuronal membranes 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 channelIon channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of all living 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 NeherErwin 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 SakmannBert Sakmann is a German cell physiologist. He shared the Nobel Prize in Physiology or Medicine with Erwin Neher in 1991 for their work on "the function of single ion channels in cells," and invention of the patch clamp...
, who developed the technique of
patch clampThe 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 structuresX-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 diffracts into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a three-dimensional picture...
,*
* fluorescence distance measurements*
* and
cryo-electron microscopyElectron cryomicroscopy is a form of electron microscopy where the sample is studied at cryogenic temperatures...
studies.*
Julius Bernstein was also the first to introduce the
Nernst equationIn electrochemistry, the Nernst equation is an equation which 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 potentialRelatively static membrane potential of quiescent cells is called resting membrane potential , as opposed to the specific dynamic electrochemical phenomenona called action potential and graded membrane potential....
across the membrane; this was generalized by
David E. GoldmanDavid E. Goldman was a scientist famous for the Goldman equation which he derived for his doctorate degree at Columbia University....
to the eponymous
Goldman equationThe 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 pumpNa+/K+-ATPase is an enzyme located in the plasma membrane in all animals.- Sodium-Potassium pumps :Active transport is responsible for the well-established observation that cells...
was identified in 1957 and its properties gradually elucidated, culminating in the determination of its atomic-resolution structure by
X-ray crystallographyX-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 diffracts into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a three-dimensional picture...
. 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 equationIn mathematics, an ordinary differential equation is a relation that contains functions of only one independent variable, and one or more of its 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 modelThe FitzHugh–Nagumo model describes a prototype of an excitable system .If the external stimulus exceeds a certain threshold value, the system will exhibit a characteristic excursion in phase space, before the variables and relax back to their rest values.This behaviour is typical for...
,* 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 computationNeural Computation is a monthly 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...
and simple
reflexA reflex action, also known as a reflex, is an involuntary and nearly instantaneous movement in response to a stimulus. In most contexts, in particular those involving humans, reflex actions are mediated via the reflex arc; this is not always true in other animals, nor does it apply to casual uses...
es, such as
escape reflexEscape 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 generators can be defined as neural networks that can endogenously produce rhythmic patterned outputs" or as "neural circuits that generate periodic motor commands for rhythmic movements such as locomotion." CPGs have been shown to produce rhythmic outputs resembling normal...
s.* Hooper, Scott L. "Central Pattern Generators." Embryonic ELS (1999) http://www.els.net/elsonline/figpage/I0000206.html (2 of 2) [2/6/2001 11:42:28 AM] Online: Accessed 27 November 2007
http://crab-lab.zool.ohiou.edu/hooper/cpg.pdf
See also
- Bursting
Bursting is a rapid signaling mode in neurons whereby clusters of two or more action potentials are emitted as a single signaling event. A burst of two spikes is called a doublet, three spikes - triplet, four - quadruplet, etc...
- Signals (biology)
- Central pattern generator
"Central pattern generators can be defined as neural networks that can endogenously produce rhythmic patterned outputs" or as "neural circuits that generate periodic motor commands for rhythmic movements such as locomotion." CPGs have been shown to produce rhythmic outputs resembling normal...
External links
Animations
- Ionic flow in action potentials at Blackwell Publishing
Wiley-Blackwell, formerly Blackwell Publishing, is a learned society publishing company based in Oxford, England. It was formed by the merger of two earlier Blackwell companies in 2001 and was taken over by John Wiley & Sons in 2007...
- Action potential propagation in myelinated and unmyelinated axons at Blackwell Publishing
Wiley-Blackwell, formerly Blackwell Publishing, is a learned society publishing company based in Oxford, England. It was formed by the merger of two earlier Blackwell companies in 2001 and was taken over by John Wiley & Sons in 2007...
- Generation of AP in cardiac cells and generation of AP in neuron cells
- Resting membrane potential from Life: The Science of Biology, by WK Purves, D Sadava, GH Orians, and HC Heller, 8th edition, New York: WH Freeman, ISBN 978-0716776710.
- Ionic motion and the Goldman voltage for arbitrary ionic concentrations at The University of Arizona
The University of Arizona is a land-grant and space-grant public institution of higher education and research located in Tucson, Arizona, United States. The University of Arizona was the first university in the state of Arizona, founded in 1885...
- A cartoon illustrating the action potential
- Action potential Propagation
Lecture notes and other materials
- The Action Potential John Kinnamon, University of Denver
The University of Denver , founded in 1864 is the oldest private university in the Rocky Mountain Region of the United States. The University of Denver is a coeducational, four-year university in Denver, Colorado. DU currently enrolls approximately 10,791 students, divided between graduate and...
- Resting and Action Membrane Potentials Teaching Resources Center, UC Davis. Animated tutorials
- Open-source software to simulate neuronal and cardiac action potentials at SourceForge.net
SourceForge is a web-based source code repository. It acts as a centralized location for software developers to control and manage open source software development. The website is operated by SourceForge, Inc. and runs a version of SourceForge Enterprise Edition, forked from the last open-source...