The Na⁺/H⁺ exchanger and pH regulation in the heart

The mammalian Na(+) /H(+) exchanger isoform 1 (NHE1) is an integral membrane protein ubiquitously expressed in mammalian cells. It is made up of two domains: a 500-amino acid membrane domain that is responsible for transport and removes protons, and a regulatory intracellular cytosolic domain made up of 315 amino acids. NHE1 is the major isoform found in the myocardium where it plays an important role in the regulation of intracellular pH by exchanging one intracellular proton for one extracellular sodium. Although NHE1 normally fulfills this important physiological role, aberrant regulation and overactivation of NHE1 contribute to heart disease, including acute ischemia reperfusion damage and cardiac hypertrophy. This review summarizes past and current knowledge of the role and regulation of NHE1 in the myocardium.