CARDIAC G(S-ALPHA) OVEREXPRESSION ENHANCES L-TYPE CALCIUM CHANNELS THROUGH AN ADENYLYL-CYCLASE INDEPENDENT PATHWAY

The alpha subunit of the stimulatory heterotrimeric G protein (G(s alp ha)) is critical for the beta-adrenergic receptor activation of the cA MP messenger system. The role of G(s alpha) in regulating cardiac Ca2 channel activity, however, remains controversial. Cultured neonatal c ardiac myocytes from transgenic mice overexpressing cardiac G(s alpha) were used to assess the role of G(s alpha) on the whole-cell Ca2+ cur rents (I-Ca) Cardiac myocytes from transgenic mice had a 490% higher p eak I-Ca compared with those of either wild-type controls or G(s alpha )-nonexpressing littermates. The effect of G(s alpha) overexpression w as mimicked by intracellular dialysis of wild-type cardiac myocytes wi th GTP gamma S-activated G(s alpha). This effect was not mediated by p rotein kinase A activation as intracellular perfusion with a protein k inase A inhibitor rendered the same degree of activation in either tra nsgenic or wild-type myocytes also dialyzed with activated G(s alpha). The data indicate that G(s alpha) overexpression is associated with a constitutive enhancement of I-Ca which is independent of the cAMP pat hway and activation of endogenous adenylyl cyclase.