Sodium/Potassium/Calcium Exchanger Family

Sodium/potassium/calcium exchanger family is also known as solute carrier family 24. Members of the SLC24 gene family encode K⁺-dependent Na⁺-Ca²⁺ exchangers (NCKX) which utilize both the inward Na⁺ and outward K⁺ gradients to extrude Ca²⁺ from cells. There are five human SLC24 genes that play a role in biological processes such as vision in retinal rod and cone photoreceptors, olfaction, skin pigmentation and at least three of the five genes are also widely expressed in the brain. Like most other solute carriers, NCKX transporters are thought to play roles via the alternating access mechanism.

Fig.1 Current topological model of NCKX proteins. (Schnetkamp, 2013)

For NCKX1 in ROS as well for NCKX2 expressed in cell lines, the transport stoichiometry was determined to be 4Na⁺:(1Ca²⁺+1K⁺). This means that Ca²⁺ extrusion from cells is driven by both inward Na⁺ and outward K⁺ gradients and is also driven by the negative inside membrane potential in view of the electrogenic nature of transport. This also means that Na⁺/Ca²⁺-K⁺ exchangers can maintain larger Ca²⁺ gradients than the NCX Na⁺/Ca²⁺ exchangers operating at a 3:1 stoichiometry. In addition, Na⁺/Ca²⁺-K⁺ exchangers do not easily reverse from the Ca²⁺ efflux mode to Ca²⁺ influx mode upon strong membrane depolarization and/or reduction of the transmembrane Na⁺ gradient when compared with the Na⁺/Ca²⁺ exchanger. This would make NCKX proteins a preferred choice for cells exhibiting long-lived depolarizations due to sustained inward Na⁺ currents which are likely to decrease the transmembrane Na⁺ gradient as well, thereby reducing two of the three components of the driving force to extrude Ca²⁺ from cells via NC(K)X exchangers. This applies to the retinal rod and cone photoreceptors, both of which operate by modulating a sustained inward Na⁺ and Ca²⁺ current carried by cGMP-gated channels.

Human SLC24 Family Members
SLC24A1	SLC24A5	SLC24A3	SLC24A4

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Reference

Schnetkamp P P, et al. (2013). The SLC24 gene family of Na⁺/Ca²⁺-K⁺ exchangers: from sight and smell to memory consolidation and skin pigmentation. Mol Aspects Med. 34(2-3): 455-64.

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