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Department of Physiology, University of Wisconsin, Madison, Wisconsin 53706
Diacylglycerol has been hypothesized to
mediate the positive inotropic response of myocardium to the
-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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