Changes in intracellular pH (pHi) can produce marked effects on cardiac function, and, therefore, it is important that the cell possess mechanisms by which pHi is regulated, especially after intracellular acidosis associated with myocardial ischemia. The Na+/H+ exchanger (NHE) and the Na+/HCO3− symport represent the 2 major pathways by which alkalinization occurs in cardiac cells. The NHE not only regulates pHi but also cell volume and intracellular signaling in response to a variety of stimuli.The NHE in mammalian myocardium1 has received considerable attention in the past decade, because it has been linked to cardiac growth and reperfusion injury.2 3 The NHE is activated by mechanical stretch in cultured cardiac myocytes and is thought to be a primary factor in influencing the anabolic state of the ventricular myocardium in response to pressure overload.4 5 Activation of the NHE occurs via phosphorylation of the cytoplasmic domain, which appears to be mediated by protein kinase C.6 Mechanical stretch of neonatal cardiac myocytes has also been associated with activation of second messengers, such as inositol triphosphate, protein kinase C, Raf-1 kinase, and mitogen-activated protein (MAP) kinase, all of which can contribute to reexpression of a number of fetal genes associated with cardiac hypertrophy, including β-myosin heavy chain, skeletal α-actin, and atrial natriuretic peptide.7 In studies using neonatal rat cardiac myocytes cultured on elastic membranes, stretch-mediated increases in MAP kinase activity and protein synthesis were attenuated by treatment of cells with the NHE antagonist Hoe 694,2 8 suggesting that the NHE has an important role in mediating growth in the pressure-overloaded myocardium.Deformation of the cardiac myocyte as it occurs in vivo, or in vitro under experimental or pathological conditions, presents a mechanical stress for cellular structures. This …
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