ROLE OF INTRACELLULAR CA2+ AND PH IN POSITIVE INOTROPIC RESPONSE OF CARDIOMYOCYTES TO DIACYLGLYCEROL

Diacylglycerol has been hypothesized to mediate the positive inotropic response of myocardium to the alpha-adrenergic agonists angiotensin I I and endothelin. The mechanism of action of diacylglycerol was examin ed here in adult rat ventricular myocytes by releasing dioctanoylglyce rol (diC(8)) intracellularly from a caged compound while monitoring Ca 2+ transients and pH with fluorescent indicators. DiC(8) caused a thre e- to fourfold increase in twitch amplitude and a twofold increase in the systolic Ca2+ transient. No other parameter was consistently influ enced by diC(8), including the kinetics of Ca2+ cycling, the Ca2+ cont ent of the sarcoplasmic reticulum, or the myofilament Ca2+ sensitivity . DiC(8) also had no detectable effect on intracellular pH or Na+/H+ a ntiport activity. Consistent with this finding, the Na+H+ exchange inh ibitor N-ethylisopropyl amiloride was without effect on the positive i notropic response to diC(8). The marked enhancement of systolic Ca2+ b y diC(8)suggests that the process of excitation-contraction coupling i s an important and possibly preferred target of diacylglycerol-protein kinase C signaling in myocardium.