AJP - Cell Physiology, Vol 263, Issue 5 C933-C940, Copyright © 1992 by American Physiological Society
Ca2+ mobilization by extracellular ATP in rat cardiac myocytes: regulation by protein kinase C and A
J. S. Zheng, A. Christie, M. N. Levy and A. Scarpa
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106.
Activation of protein kinase C (PKC) modulates the mobilization of
intracellular Ca2+ induced by extracellular ATP in rat ventricular
myocytes. Pretreatment of myocytes with PKC activators attenuated both the
ATP-induced Ca2+ transient and the noradrenergic potentiation of the Ca2+
response. Various PKC activators decreased both the basal cAMP level and
the cAMP levels that had been elevated by norepinephrine, forskolin, or
3-isobutyl-1-methylxanthine. The inhibitory effects of PKC activators were
reversed by the PKC inhibitor staurosporine. The ATP-induced Ca2+ response
is an integrated response resulting from ATP eliciting an inward cation
current (IATP), cellular depolarization, Ca2+ influx through Ca2+ channels,
and Ca2+ release from the sarcoplasmic reticulum. We used the whole cell
voltage-clamp technique to investigate which steps of this integrated
response are affected by PKC. PKC activators did not significantly affect
the IATP. In contrast, PKC activators decreased the basal Ca2+ current
(ICa) or Ba2+ current and the beta-adrenergic-stimulated ICa. These results
suggest that PKC-induced suppression of the ATP-induced Ca2+ response and
the beta-adrenergic-potentiated Ca2+ response is achieved at least
partially by decreasing the intracellular cAMP level and ICa.
