Divergent Effects of Receptor- and Nonreceptor-Mediated Activators of Sodium-Hydrogen Exchange on Reperfusion-Induced Contractile Dysfunction
The regulation of intracellular pH in the cardiac cell is critical for the normal maintenance of cell function, particularly since protons are continuosly generated through various cellular processes. As changes in intracellular pH could profoundly affect cell function, the cardiac cell possesses numerous mechanisms for maintaining pH homeostasis. Among these, the sodium-hydrogen exchanger (NHE) plays an important role for pH regulation by extruding protons in exchange for sodium influx . The exchanger is electroneutral, exchanging one H+ for one Na+. The acute regulation of NHE is under the control of various factors, although the pH gradient across the cardiac sarcolemma is likely the most critical. In addition, phosphorylation of the exchanger by protein kinase C (PKC) and other kinases results in the activation of the antiport. Thus, intracellular acidosis under conditions of normal extracellular pH represents a potent stimulus for NHE activation. In addition, direct activation of PKC or receptor-mediated stimulation of phosphoinositide hydrolysis, which results in increased production of diacylglycerol and subsequent PKC stimulation, both represent processes that result in NHE activation.
KeywordsPhorbol Ester Positive Inotropic Effect Reperfused Myocardium Intracellular Acidosis Myocardial Reperfusion Injury
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