Role of intracellular Ca21 and pH in positive inotropic response of cardiomyocytes to diacylglycerol

Pi, YeQing, and Jeffery W. Walker. Role of intracellular Ca21 and pH in positive inotropic response of cardiomyocytes to diacylglycerol. Am. J. Physiol. 275 (Heart Circ. Physiol. 44): H1473–H1481, 1998.—Diacylglycerol has been hypothesized to mediate the positive inotropic response of myocardium to the a-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 Ca21 transients and pH with fluorescent indicators. DiC8 caused a threeto fourfold increase in twitch amplitude and a twofold increase in the systolic Ca21 transient. No other parameter was consistently influenced by diC8, including the kinetics of Ca21 cycling, the Ca21 content of the sarcoplasmic reticulum, or the myofilament Ca21 sensitivity. DiC8 also had no detectable effect on intracellular pH or Na1/H1 antiport activity. Consistent with this finding, the Na1/H1 exchange inhibitor N-ethylisopropyl amiloride was without effect on the positive inotropic response to diC8. The marked enhancement of systolic Ca21 by diC8 suggests that the process of excitation-contraction coupling is an important and possibly preferred target of diacylglycerolprotein kinase C signaling in myocardium.