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

Activation of G(alpha s) via beta-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 G(alpha s) has been proposed but remains controversial. We demonstrate that, in Xenopus oocytes, antisense knockdown of endogenous G(alpha s) reduced, whereas coexpression of G(alpha s) enhanced, currents via expressed cardiac L-type channels, independently of the presence of the auxiliary subunits alpha(2)/delta or beta(2A). Coexpression of G(alpha s) did not increase the amount of alpha(1C) protein in whole oocytes or in the plasma membrane (measured immunochemically). Activation of coexpressed beta 2 adrenergic receptors did not cause a detectable enhancement of channel activity; rather, a small cAMP-dependent decrease nas observed, We conclude that coexpression of G(alpha s), but not its acute activation via beta-adrenergic receptors, enhances the activity of the cardiac L-type Ca2+ channel via a PKA-independent effect on the alpha(1C) subunit, (C) 1999 Federation of European Biochemical Societies.