Modulation of cardiac Ca²⁺ channels in Xenopus oocytes by protein kinase C

L-Type calcium channel was expressed in Xenopus laevis oocytes injected with RNAs coding for different cardiac Cu²⁺ channel subunits, or with total heart RNA. The effects of activation of protein kinase C (PKC) by the phorbol ester PMA (4β-phorbol 12-myristate 13-acetate) were studied. Currents through channels composed of the main (α₁) subunit alone were initially increased and then decreased by PMA. A similar biphasic modulation was observed when the α₁ subunit was expressed in combination with α₂/δ, β and/or γ subunits, and when the channels were expressed following injection of total rat heart RNA. No effects on the voltage dependence of activation were observed. The effects of PMA were blocked by staurosporine, a protein kinase inhibitor. β subunit moderated the enhancement caused by PMA. We conclude that both enhancement and inhibition of cardiac L-type Ca²⁺ currents by PKC are mediated via an effect on the α₁ subunit, while the β subunit may play a mild modulatory role.