Sodium-calcium exchanger
Encyclopedia
The sodium-calcium exchanger (often denoted Na+/Ca2+ exchanger, NCX, or exchange protein) is an antiporter
membrane protein
that removes calcium
from cells. It uses the energy that is stored in the electrochemical gradient
of sodium (Na+) by allowing Na+ to flow down its gradient across the plasma membrane in exchange for the countertransport of calcium
ions (Ca2+). The NCX removes a single calcium ion in exchange for the import of three sodium ions. The exchanger exists in many different cell types and animal species. The NCX is considered one of the most important cellular mechanisms for removing Ca2+.
The exchanger is usually found in the plasma membranes and the mitochondria and endoplasmic reticulum
of excitable cells.
s rapidly (has a high capacity), transporting up to five thousand Ca2+ ions per second. Therefore, it requires large concentrations of Ca2+ to be effective, but is useful for ridding the cell of large amounts of Ca2+ in a short time, as is needed in a neuron
after an action potential
. Thus, the exchanger also likely plays an important role in regaining the cell's normal calcium concentrations after an excitotoxic
insult. Another, more ubiquitous transmembrane pump that exports calcium from the cell
is the Plasma membrane Ca2+ ATPase (PMCA), which has a much higher affinity but a much lower capacity. Since the PMCA is capable of effectively binding to Ca2+ even when its concentrations are quite low, it is better suited to the task of maintaining the very low concentrations of calcium that are normally within a cell. Therefore the activities of the NCX and the PMCA complement each other.
The exchanger is involved in a variety of cell functions including the following:
. In addition, as with other transport proteins, the amount and direction of transport depends on transmembrane substrate gradients. This fact can be protective because increases in intracellular Ca2+ concentration that occur in excitotoxicity may activate the exchanger in the forward direction even in the presence of a lowered extracellular Na+ concentration. However, it also means that, when intracellular levels of Na+ rise beyond a critical point, the NCX begins importing Ca2+ The NCX may operate in both forward and reverse directions simultaneously in different areas of the cell, depending on the combined effects of Na+ and Ca2+ gradients.
Antiporter
An antiporter is an integral membrane protein involved in secondary active transport of two or more different molecules or ions across a phospholipid membrane such as the plasma membrane in opposite directions.In secondary active transport, one species of solute moves along its electrochemical...
membrane protein
Membrane protein
A membrane protein is a protein molecule that is attached to, or associated with the membrane of a cell or an organelle. More than half of all proteins interact with membranes.-Function:...
that removes calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
from cells. It uses the energy that is stored in the electrochemical gradient
Electrochemical gradient
An electrochemical gradient is a spatial variation of both electrical potential and chemical concentration across a membrane; that is, a combination of the membrane potential and the pH gradient...
of sodium (Na+) by allowing Na+ to flow down its gradient across the plasma membrane in exchange for the countertransport of calcium
Calcium in biology
Calcium plays a pivotal role in the physiology and biochemistry of organisms and the cell. It plays an important role in signal transduction pathways, where it acts as a second messenger, in neurotransmitter release from neurons, contraction of all muscle cell types, and fertilization...
ions (Ca2+). The NCX removes a single calcium ion in exchange for the import of three sodium ions. The exchanger exists in many different cell types and animal species. The NCX is considered one of the most important cellular mechanisms for removing Ca2+.
The exchanger is usually found in the plasma membranes and the mitochondria and endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
of excitable cells.
Function
The Na+/Ca2+ exchanger does not bind very tightly to Ca2+ (has a low affinity), but it can transport the ionIon
An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...
s rapidly (has a high capacity), transporting up to five thousand Ca2+ ions per second. Therefore, it requires large concentrations of Ca2+ to be effective, but is useful for ridding the cell of large amounts of Ca2+ in a short time, as is needed in a neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
after an action potential
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...
. Thus, the exchanger also likely plays an important role in regaining the cell's normal calcium concentrations after an excitotoxic
Excitotoxicity
Excitotoxicity is the pathological process by which nerve cells are damaged and killed by excessive stimulation by neurotransmitters such as glutamate and similar substances. This occurs when receptors for the excitatory neurotransmitter glutamate such as the NMDA receptor and AMPA receptor are...
insult. Another, more ubiquitous transmembrane pump that exports calcium from the cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
is the Plasma membrane Ca2+ ATPase (PMCA), which has a much higher affinity but a much lower capacity. Since the PMCA is capable of effectively binding to Ca2+ even when its concentrations are quite low, it is better suited to the task of maintaining the very low concentrations of calcium that are normally within a cell. Therefore the activities of the NCX and the PMCA complement each other.
The exchanger is involved in a variety of cell functions including the following:
- control of neurosecretionNeurosecretionNeurosecretion is the synthesis and release of hormones from neurons. These hormones are normally secreted from nerve cells in the brain that then circulate into the blood. These neurohormones are similar to nonneural endocrine cells and glands in that they also regulate both endocrine and...
- activity of photoreceptor cells
- cardiac muscleCardiac muscleCardiac muscle is a type of involuntary striated muscle found in the walls and histologic foundation of the heart, specifically the myocardium. Cardiac muscle is one of three major types of muscle, the others being skeletal and smooth muscle...
relaxation - maintenance of Ca2+ concentration in the sarcoplasmic reticulum in cardiac cells
- maintenance of Ca2+ concentration in the endoplasmic reticulum of both excitable and nonexcitable cells
- excitation-contraction couplingExcitation-contraction couplingExcitation-contraction coupling is a term coined in 1952 to describe the physiological process of converting an electrical stimulus to a mechanical response . This process is fundamental to muscle physiology, whereby the electrical stimulus is usually an action potential and the mechanical...
- maintenance of low Ca2+ concentration in the mitochondria
Reversibility
Since the transport is electrogenic (alters the membrane potential), depolarization of the membrane can reverse the exchanger's direction if the cell is depolarized enough, as may occur in excitotoxicityExcitotoxicity
Excitotoxicity is the pathological process by which nerve cells are damaged and killed by excessive stimulation by neurotransmitters such as glutamate and similar substances. This occurs when receptors for the excitatory neurotransmitter glutamate such as the NMDA receptor and AMPA receptor are...
. In addition, as with other transport proteins, the amount and direction of transport depends on transmembrane substrate gradients. This fact can be protective because increases in intracellular Ca2+ concentration that occur in excitotoxicity may activate the exchanger in the forward direction even in the presence of a lowered extracellular Na+ concentration. However, it also means that, when intracellular levels of Na+ rise beyond a critical point, the NCX begins importing Ca2+ The NCX may operate in both forward and reverse directions simultaneously in different areas of the cell, depending on the combined effects of Na+ and Ca2+ gradients.
History
In 1968, H Reuter and N Seitz published findings that, when Na+ is removed from the medium surrounding a cell, the efflux of Ca2+ is inhibited, and they proposed that there might be a mechanism for exchanging the two ions. In 1969, a group led by PF Baker that was experimenting using squid axons published a finding that propsed that there exists a means of Na+ exit from cells other than the sodium-potassium pump.See also
- Active transportActive transportActive transport is the movement of a substance against its concentration gradient . In all cells, this is usually concerned with accumulating high concentrations of molecules that the cell needs, such as ions, glucose, and amino acids. If the process uses chemical energy, such as from adenosine...
- Cardiac action potentialCardiac action potentialIn electrocardiography, the cardiac action potential is a specialized action potential in the heart, necessary for the electrical conduction system of the heart....
- Potassium-dependent sodium-calcium exchangerPotassium-dependent sodium-calcium exchangerPotassium-dependent sodium-calcium exchanger also known as solute carrier family 24 is a type of sodium-calcium exchanger that requires potassium to function.- Family members :...
External links
- Diagram at cvphysiology.com
- Klabunde, RE. 2007. Cardiovascular Physiology Concepts: Calcium Exchange.