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 diacylglycerol (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.