Cardiac G(sα) overexpression enhances L-type calcium channels through an adenylyl cyclase independent pathway

The α subunit of the stimulatory heterotrimeric G protein (G(sα)) is critical for the β-adrenergic receptor activation of the cAMP messenger system. The role of G(sα) in regulating cardiac Ca(2+) channel activity, however, remains controversial. Cultured neonatal cardiac myocytes from transgenic mice overexpressing cardiac G(sα) were used to assess the role of G(sα) on the whole-cell Ca(2+) currents (I(Ca)). Cardiac myocytes from transgenic mice had a 490% higher peak I(Ca) compared with those of either wild-type controls or G(sα)-nonexpressing littermates. The effect of G(sα) overexpression was mimicked by intracellular dialysis of wild-type cardiac myocytes with GTPγS-activated G(sα). This effect was not mediated by protein kinase A activation as intracellular perfusion with a protein kinase A inhibitor rendered the same degree of activation in either transgenic or wild-type myocytes also dialyzed with activated G(sα). The data indicate that G(sα) overexpression is associated with a constitutive enhancement of I(Ca) which is independent of the cAMP pathway and activation of endogenous adenylyl cyclase.