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).