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 Ca2+ channel subunits, or with total heart RNA. The effects of activation of protein kinase C (PKC) by the phorbol ester PMA (4-beta-phorbol 12-myristate 13-acetate) were studied. Currents through channels composed of the main (alpha-1) subunit alone were initially increased and then decreased by PMA. A similar biphasic modulation was observed when the alpha-1 subunit was expressed in combination with alpha-2/delta, beta and/or gamma-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. beta-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 alpha-1 subunit, while the beta-subunit may play a mild modulatory role.