Regulation of myocardial Na+/H+ exchanger activity

The Na+/H+ exchanger is a plasma membrane protein, present in the myocardiu m, which removes intracellular protons and exchanges them with extracellula r Na+. The protein comprises an N-terminal, hydrophobic, integral membrane domain that transports the ions and a C-terminal, hydrophilic region that r egulates the N-terminal domain. The C-terminal domain has several sub-domai ns, including one region that binds calmodulin and another that is phosphor ylated by protein kinases. The Na+/H+ exchanger is activated by angiotensin , endothelin and alpha (1)-adrenergic stimulation. These effectors increase phosphorylation of the C-terminal domain by protein kinases, and G protein s have been implicated in this, but their role remains to be defined. It ha s recently been shown that ischemia and other stimuli lead to an increased expression of the Na+/H+ exchanger in the myocardium. The role of this incr eased expression in the pathology of ischemia and reperfusion-mediated myoc ardial damage has yet to be determined. Recent evidence suggests that the N a+/H+ exchanger may play a key role in hypertrophy of the myocardium, and t hat its activation through G protein-coupled receptors may be important in mediating its effects.