The Na(+)-Ca(2+) exchanger (NCX) links transmembrane movements of Ca(2+) ions to the reciprocal movement of Na(+) ions. It normally functions primarily as a Ca(2+) efflux mechanism in excitable tissues such as the heart, but it can also mediate Ca(2+) influx under certain conditions. Na(+) and Ca(2+) ions exert complex regulatory effects on NCX activity. Ca(2+) binds to two regulatory sites in the exchanger's central hydrophilic domain, and this interaction is normally essential for activation of exchange activity. High cytosolic Na(+) concentrations, however, can induce a constitutive activity that by-passes the need for allosteric Ca(2+) activation. Constitutive NCX activity can also be induced by high levels of phopshotidylinositol-4,5-bisphosphate (PIP₂) and by mutations affecting the regulatory calcium binding domains. In addition to promoting constitutive activity, high cytosolic Na(+) concentrations also induce an inactivated state of the exchanger (Na(+)-dependent inactivation) that becomes dominant when cytosolic pH and PIP₂ levels fall. Na(+)-dependent inactivation may provide a means of protecting cells from Ca(2+) overload due to NCX-mediated Ca(2+) influx during ischemia.

中文翻译：

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心脏钠钙交换剂的离子调节。

Na（+）-Ca（2+）交换剂（NCX）将Ca（2+）离子的跨膜运动链接到Na（+）离子的往复运动。它通常主要用作可兴奋性组织（如心脏）中的Ca（2+）外排机制，但在某些条件下它也可以介导Ca（2+）流入。Na（+）和Ca（2+）离子对NCX活性发挥复杂的调节作用。Ca（2+）绑定到交换器的中央亲水域中的两个调节位点，这种相互作用通常对于激活交换活性至关重要。高的胞质Na（+）浓度，但是，可以诱导构成活性，从而绕过变构Ca（2+）激活的需要。高水平的磷脂酰肌醇-4,5-双磷酸酯（PIP 2）和影响调节钙结合结构域的突变也可以诱导NCX的组成活性。除了促进组成性活性外，高的胞质Na（+）浓度还诱导了交换子的失活状态（依赖Na（+）的失活），当细胞质的pH和PIP 2含量下降时，这种状态就占主导地位。Na（+）依赖的失活可以提供一种保护细胞免受Ca（2+）超负荷的手段，由于NCX介导的Ca（2+）缺血期间大量涌入。