Regulation of cardiac L-type Ca2+ channel by coexpression of Gαs in Xenopus oocytes

Activation of Gαs via β-adrenergic receptors enhances the activity of cardiac voltage-dependent Ca2+ channels of the L-type, mainly via protein kinase A (PKA)-dependent phosphorylation. Contribution of a PKA-independent effect of Gαs has been proposed but remains controversial. We demonstrate that, in Xenopus oocytes, antisense knockdown of endogenous Gαs reduced, whereas coexpression of Gαs enhanced, currents via expressed cardiac L-type channels, independently of the presence of the auxiliary subunits α2/δ or β2A. Coexpression of Gαs did not increase the amount of α1C protein in whole oocytes or in the plasma membrane (measured immunochemically). Activation of coexpressed β2 adrenergic receptors did not cause a detectable enhancement of channel activity; rather, a small cAMP-dependent decrease was observed. We conclude that coexpression of Gαs, but not its acute activation via β-adrenergic receptors, enhances the activity of the cardiac L-type Ca2+ channel via a PKA-independent effect on the α1C subunit.