AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol 275: H1473-H1481, 1998;
0363-6135/98 $5.00
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Vol. 275, Issue 4, H1473-H1481, October 1998

Role of intracellular Ca2+ and pH in positive inotropic response of cardiomyocytes to diacylglycerol

Yeqing Pi and Jeffery W. Walker

Department of Physiology, University of Wisconsin, Madison, Wisconsin 53706

Diacylglycerol has been hypothesized to mediate the positive inotropic response of myocardium to the alpha -adrenergic agonists angiotensin II and endothelin. The mechanism of action of diacylglycerol was examined here in adult rat ventricular myocytes by releasing dioctanoylglycerol (diC8) intracellularly from a caged compound while monitoring Ca2+ transients and pH with fluorescent indicators. DiC8 caused a three- to fourfold increase in twitch amplitude and a twofold increase in the systolic Ca2+ transient. No other parameter was consistently influenced by diC8, including the kinetics of Ca2+ cycling, the Ca2+ content of the sarcoplasmic reticulum, or the myofilament Ca2+ sensitivity. DiC8 also had no detectable effect on intracellular pH or Na+/H+ antiport activity. Consistent with this finding, the Na+/H+ exchange inhibitor N-ethylisopropyl amiloride was without effect on the positive inotropic response to diC8. The marked enhancement of systolic Ca2+ by diC8 suggests that the process of excitation-contraction coupling is an important and possibly preferred target of diacylglycerol-protein kinase C signaling in myocardium.

excitation-contraction coupling; fluorescent indicators; ventricular cells; sodium/hydrogen antiport


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