Sodium-calcium exchanger

Sodium-calcium exchanger
solute carrier family 8 (sodium/calcium exchanger), member 1
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
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
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]



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]

See also


  1. ^ a b c d e f Yu, SP; Choi, DW (1997). "Na+–Ca2+ exchange currents in cortical neurons: concomitant forward and reverse operation and effect of glutamate". European Journal of Neuroscience 9 (6): 1273–81. doi:10.1111/j.1460-9568.1997.tb01482.x. PMID 9215711. 
  2. ^ a b c d e Dipolo, R; Beaugé, L (2006). "Sodium/calcium exchanger: Influence of metabolic regulation on ion carrier interactions". Physiological Reviews 86 (1): 155–203. doi:10.1152/physrev.00018.2005. PMID 16371597. 
  3. ^ a b Kiedrowski, L; Brooker, G; Costa, E; Wroblewski, JT (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. 
  4. ^ Patterson M, Sneyd J, Friel DD (January 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. 
  5. ^ Carafoli, E; Santella, L; Branca, D; Brini, M. (2001). "Generation, control, and processing of cellular calcium signals". Critical Reviews in Biochemistry and Molecular Biology 36 (2): 107–260. doi:10.1080/20014091074183. PMID 11370791. 
  6. ^ Siegel, GJ; Agranoff, BW; Albers, RW; Fisher, SK; Uhler, MD, editors (1999). Basic Neurochemistry: Molecular, Cellular, and Medical Aspects (6th ed.). Philadelphia: Lippincott,Williams & Wilkins. ISBN 078170104X. 
  7. ^ Bindokas, VP; Miller, RJ (1995). "Excitotoxic degeneration is initiated at non-random sites in cultured rat cerebellar neurons". Journal of Neuroscience 15 (11): 6999–7011. PMID 7472456. 
  8. ^ Wolf, JA; Stys, PK; Lusardi, T; Meaney, D; Smith, DH (2001). "Traumatic Axonal Injury Induces Calcium Influx Modulated by Tetrodotoxin-Sensitive Sodium Channels". Journal of Neuroscience 21 (6): 1923–30. PMID 11245677. 
  9. ^ Reuter H, Seitz N (March 1968). "The dependence of calcium efflux from cardiac muscle on temperature and external ion composition". J. Physiol. (Lond.) 195 (2): 451–70. PMC 1351672. PMID 5647333. 
  10. ^ Baker PF, Blaustein MP, Hodgkin AL, Steinhardt RA (February 1969). "The influence of calcium on sodium efflux in squid axons". J. Physiol. (Lond.) 200 (2): 431–58. PMC 1350476. PMID 5764407. 

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