Regulation of the Na+/H+ exchanger in the healthy and diseased myocardium

Background: Na+/H+ exchangers (NHE's) are membrane proteins that regulate ion fluxes, they extrude one intracellular proton in exchange for one extracellular sodium thereby regulating intracellular pH. Mammalian NHE's have nine isoforms, NHE1-NHE9. NHE1 is present in all mammalian cell and is the only isoform present in cardiomyocytes. NHE1 contributes to damage to the myocardium with ischemia and reperfusion and to heart hypertrophy. Objective: To summarize the current state of knowledge with regard to regulation of NHE1 in the myocardium. Methods: A review of relevant literature. Results: Inhibition of NHE reduces ischemia-reperfusion damage and development of hypertrophy. Extracellular-signal-regulated kinase (ERK)-dependent phosphorylation activates NHE1 in the myocardium. Ischemia and subsequent reperfusion activates the ERK-dependent pathway and may lead to aggravation of damage. Conclusions: Elucidation of the regulatory pathway of NHE1 in the myocardium could lead to novel approaches to reduce heart hypertrophy and ischemia-reperfusion damage.