Regulation of cardiac L-type Ca2+ channel by coexpression of G(alpha s) inXenopus oocytes

Activation of G(alpha s) via beta-adrenergic receptors enhances the activit y of cardiac voltage-dependent Ca2+ channels of the L-type, mainly via prot ein kinase A (PKA)-dependent phosphorylation. Contribution of a PKA-indepen dent effect of G(alpha s) has been proposed but remains controversial. We d emonstrate that, in Xenopus oocytes, antisense knockdown of endogenous G(al pha s) reduced, whereas coexpression of G(alpha s) enhanced, currents via e xpressed cardiac L-type channels, independently of the presence of the auxi liary subunits alpha(2)/delta or beta(2A). Coexpression of G(alpha s) did n ot increase the amount of alpha(1C) protein in whole oocytes or in the plas ma membrane (measured immunochemically). Activation of coexpressed beta 2 a drenergic receptors did not cause a detectable enhancement of channel activ ity; rather, a small cAMP-dependent decrease nas observed, We conclude that coexpression of G(alpha s), but not its acute activation via beta-adrenerg ic 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 E uropean Biochemical Societies.