Ca2+ mobilization by extracellular ATP in rat cardiac myocytes: regulation by protein kinase C and A.
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.
Zheng
J S
JS
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106.
Christie
A
A
Levy
M N
MN
Scarpa
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004594:Electrophysiology; D005110:Extracellular Space / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D007425:Intracellular Membranes / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology*; D051381:Rats
D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D011494:Protein Kinases; D011493:Protein Kinase C; D002118:Calcium