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Ca2+ plays a critical role in intracellular signaling and thus regulation of calcium balance is critical for the maintenance of this signaling function. The plasma membrane Na+/Ca2+ (NaCX) exchangers mediate Na+-dependent Ca2+ efflux in a wide variety of cell types. NaCX can move Ca2+ either into or out of cells, depending on the net Na+, Ca2+, and K+ gradient across the membrane. In mammals, at least 5 distinct genes code for the exchangers: Three NaCX (NaCX-1, NaCX-2, and NaCX-3), and two in the NaCKX family (NaCKX-1 and NaCKX-2). NaCX-1 is most prominently expressed in the heart where it plays a major role in excitation-contraction coupling (Matsuoka et al., 1993). NACX-1 may also be a target for protection of the heart and brain from ischemia and reperfusion injury (Hagihara et al., 2005; Bano et al., 2005; Choi, 2005).
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