Reactome | SLC8A1,2,3 exchange 3Na+ for Ca2+

SLC8A1,2,3 exchange 3Na+ for Ca2+

Stable Identifier

R-HSA-425661

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, cytosol, extracellular region

ReviewStatus

5/5

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The sodium/calcium exchangers 1, 2 and 3 (SCL8A1,2,3 aka NCX1,2,3) belong to one of three families that control Ca2+ flux across the plasma membrane or intracellular compartments. They extrude Ca2+ from the cell, using the electrochemical gradient of Na+ as it flows into the cell. One Ca2+ is exchanged for three Na+. During this electrogenic exchange, the membrane potential is altered. SLC8A1, 2, 3 play a minor role during phase 2, since they begin to restore ion concentrations. The high concentration of intracellular calcium starts contraction of those cells, which is sustained in the plateau phase. SLC8A1 has a ubiquitous expression profile (highest expression in heart, brain and kidney) and was originally cloned and characterized from human cardiac muscle (Komuro et al. 1992). Both SLC8A2) (Li et al. 1994) and SLC8A3 (Gabellini et al. 2002) are expressed in the brain.
In Rabbits, sorcin (SRI) activates SLC8A1, via the interaction of the respective Ca2+-binding domains (Zamparelli et al. 2010). Calmodulin (CALM1) binds to the cytoplasmic loop of NCX1 to negatively regulate exchange activity (Chou et al. 2015).

Literature References

PubMed ID	Title	Journal	Year
1374913	Molecular cloning and characterization of the human cardiac Na+/Ca2+ exchanger cDNA Komuro, I, Wenninger, KE, Philipson, KD, Izumo, S	Proc Natl Acad Sci U S A	1992
20298697	Activation of the cardiac Na(+)-Ca(2+) exchanger by sorcin via the interaction of the respective Ca(2+)-binding domains Zamparelli, C, Macquaide, N, Colotti, G, Verzili, D, Seidler, T, Smith, GL, Chiancone, E	J. Mol. Cell. Cardiol.	2010
8021246	Cloning of the NCX2 isoform of the plasma membrane Na(+)-Ca2+ exchanger Li, Z, Matsuoka, S, Hryshko, LV, Nicoll, DA, Bersohn, MM, Burke, EP, Lifton, RP, Philipson, KD	J Biol Chem	1994
26421717	Calmodulin Interacts with the Sodium/Calcium Exchanger NCX1 to Regulate Activity Chou, AC, Ju, YT, Pan, CY	PLoS ONE	2015
12406570	The human SLC8A3 gene and the tissue-specific Na+/Ca2+ exchanger 3 isoforms Gabellini, N, Bortoluzzi, S, Danieli, GA, Carafoli, E	Gene	2002