Sodium calcium exchanger
| 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 |
Overview
The sodium-calcium exchanger (often denoted Na+/Ca2+ exchanger, NCX, or exchange protein) is an antiporter membrane protein which 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, like 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]
History
In 1968, H Reuter and N Sinz 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 there existed a means of Na+ exit from cells other than the sodium-potassium pump.[2][10]
See also
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Yu, SP (1997). "Na+–Ca2+ exchange currents in cortical neurons: concomitant forward and reverse operation and effect of glutamate". European Journal of Neuroscience. 9 (6): 1273–1281. doi:10.1111/j.1460-9568.1997.tb01482.x. PMID 9215711. Unknown parameter
|coauthors=ignored (help);|access-date=requires|url=(help) - ↑ 2.0 2.1 2.2 2.3 2.4 Dipolo, R; Beaugé, L (2006). "Sodium/calcium exchanger: Influence of metabolic regulation on ion carrier interactions" Physiological Reviews 86 (1): 155-203. PMID 16371597. Retrieved on August 29, 2007.
- ↑ 3.0 3.1 Kiedrowski, L (1994). "Glutamate impairs neuronal calcium extrusion while reducing sodium gradient". Neuron. 12 (2): 295–300. doi:10.1016/0896-6273(94)90272-0. PMID 7906528. Unknown parameter
|coauthors=ignored (help);|access-date=requires|url=(help) - ↑ Patterson M, Sneyd J, Friel DD (2007). "Depolarization-induced calcium responses in sympathetic neurons: relative contributions from Ca2+ entry, extrusion, ER/mitochondrial Ca2+ uptake and release, and Ca2+ buffering". J. Gen. Physiol. 129 (1): 29–56. doi:10.1085/jgp.200609660. PMC 2151609. PMID 17190902. Unknown parameter
|month=ignored (help) - ↑ Carafoli, E (2001). "Generation, control, and processing of cellular calcium signals". Critical Reviews in Biochemistry and Molecular Biology. 36 (2): 107–260. doi:10.1080/20014091074183. Retrieved 2007-01-09. Unknown parameter
|coauthors=ignored (help) - ↑ Siegel, GJ (1999). Basic Neurochemistry: Molecular, Cellular, and Medical Aspects. 6th ed. Philadelphia: Lippincott,Williams & Wilkins. Unknown parameter
|coauthors=ignored (help) - ↑ Bindokas, VP (1995). "Excitotoxic degeneration is initiated at non-random sites in cultured rat cerebellar neurons". Journal of Neuroscience. 15 (11): 6999–7011. PMID 7472456. Retrieved 2007-01-15. Unknown parameter
|coauthors=ignored (help) - ↑ Wolf, JA (2001). "Traumatic Axonal Injury Induces Calcium Influx Modulated by Tetrodotoxin-Sensitive Sodium Channels". Journal of Neuroscience. 21 (6): 1923–1930. PMID 11245677. Retrieved 2007-01-15. Unknown parameter
|coauthors=ignored (help) - ↑ Reuter, H; Seitz, N (1968). "The dependence of calcium efflux from cardiac muscle on temperature and external ion composition." 195 (2): 451-470. PMID 5647333. Retrieved on August 29, 2007.
- ↑ Baker, PF; Blaustein, MP; Hodgkin, AL; and Steinhardt (1969). The influence of calcium on sodium efflux in squid axons". Journal of Physiology 200 (2): 431-458. Retrieved on August 29, 2007.
External links
- Sodium-calcium+exchanger at the US National Library of Medicine Medical Subject Headings (MeSH)
- Diagram at cvphysiology.com
- Klabunde, RE. 2007. Cardiovascular Physiology Concepts: Calcium Exchange.