Sodium-calcium exchanger

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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 membranes of endoplasmic reticulum of excitable cells.^[3]

[edit] 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.^[4] 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.^[5] 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

[edit] 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 Ca^2+[1][6][7] 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]

[edit] 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][8] 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][9]

[edit] See also

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

[edit] References

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): 1273–1281. 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. PMID 16371597. Retrieved on August 29, 2007.
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. PMID 7906528. 
4. ^ 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. 
5. ^ 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. 
6. ^ 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. 
7. ^ 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): 1923–1930. PMID 11245677. 
8. ^ 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.
9. ^ 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.

[edit] External links

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