Protein kinase C regulation of cardiac calcium channels expressed in Xenopus oocytes.
L-Type cardiac Ca2+ channels expressed in Xenopus oocyte were studied following rat heart ribonucleic acid, messenger (mRNA) injection. We demonstrate that exogenous Ca2+ channels are sensitive to intracellular regulation by protein kinase C (PKC). This was performed by using two types of PKC activators [phorbol esters and a structural analogue of diacyl-glycerol (DAG)] and a specific peptidic inhibitor. Ca2+ channel modulation resulted in an initial increase of the inward current, without any modification of the voltage-dependent properties, and a second delayed phase, specifically observed with phorbol esters, characterized by a progressive decrease in current amplitude. Concomitantly, a reduction of membrane capacitance, reflecting a reduction of the total membrane surface area, was observed. We suggest that this phenomenon underlies the irreversible decrease of the expressed Ba2+ current via sequestration of Ca2+ channels and/or PKC. We also demonstrate that regulation of cardiac mRNA-directed Ca2+ channels by PKC activators was strictly dependent on intracellular Ca2+ concentration, and was partially additive with cyclic-adenosine-monophosphate-(cAMP) dependent regulation.
Bourinet
E
E
Centre de Recherches de Biochimie Macromoleculaire, CNRS UPR 9008, INSERM U 249, Montpellier, France.
Fournier
F
F
Lory
P
P
Charnet
P
P
Nargeot
J
J
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004594:Electrophysiology; D004789:Enzyme Activation / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014981:Xenopus
D015220:Calcium Channels; D004075:Diglycerides; D012333:RNA, Messenger; D015240:Phorbol 12,13-Dibutyrate; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate