Sodium-calcium exchanger

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.^[1] The exchanger exists in many different cell types and animal species.^[2] The NCX is considered one of the most important cellular mechanisms for removing Ca²⁺.^[2]

The exchanger is usually found in the plasma membranes and the mitochondria and endoplasmic reticulum of excitable cells.^[3][4]

Function

The Na⁺/Ca²⁺ exchanger does not bind very tightly to Ca²⁺ (has a low affinity), but it can transport the ions rapidly (has a high capacity), transporting up to five thousand Ca²⁺ ions per second.^[5] 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.^[3] 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.^[6] 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:^[2]

• control of neurosecretion
• activity of photoreceptor cells
• cardiac 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 coupling
• 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 excitotoxicity.^[1] In addition, as with other transport proteins, the amount and direction of transport depends on transmembrane substrate gradients.^[1] 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.^[1] However, it also means that, when intracellular levels of Na⁺ rise beyond a critical point, the NCX begins importing Ca^2+[1][7][8] 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.^[1]

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.^[2][9] 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.^[2][10]

See also

• Active transport
• Cardiac action potential
• Potassium-dependent sodium-calcium exchanger

References

External links

• MeSH Sodium-calcium+exchanger
• Diagram at cvphysiology.com
• Klabunde, RE. 2007. Cardiovascular Physiology Concepts: Calcium Exchange.