| solute carrier family 8 (sodium/calcium exchanger), member 1 | |
|---|---|
| Identifiers | |
| Symbol | SLC8A1 |
| Alt. symbols | NCX1 |
| Entrez | 6546 |
| HUGO | 11068 |
| OMIM | 182305 |
| RefSeq | NM_021097 |
| UniProt | P32418 |
| Other data | |
| Locus | Chr. 2 p23-p21 |
| solute carrier family 8 (sodium-calcium exchanger), member 2 | |
|---|---|
| Identifiers | |
| Symbol | SLC8A2 |
| Entrez | 6543 |
| HUGO | 11069 |
| OMIM | 601901 |
| RefSeq | NM_015063 |
| UniProt | Q9UPR5 |
| Other data | |
| Locus | Chr. 19 q13.2 |
| solute carrier family 8 (sodium-calcium exchanger), member 3 | |
|---|---|
| Identifiers | |
| Symbol | SLC8A3 |
| Entrez | 6547 |
| HUGO | 11070 |
| OMIM | 607991 |
| RefSeq | NM_033262 |
| UniProt | P57103 |
| Other data | |
| Locus | Chr. 14 q24.1 |
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]
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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]
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 Ca2+[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]
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]
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