Cardiac Gsα overexpression enhances L-type calcium channels through an adenylyl cyclase independent pathway

The alpha subunit of the stimulatory heterotrimeric G protein (G(s alpha)) is critical for the beta-adrenergic receptor activation of the cAMP messenger system. The role of G(s alpha) in regulating cardiac Ca2+ channel activity, however, remains controversial. Cultured neonatal cardiac myocytes from transgenic mice overexpressing cardiac G(s alpha) were used to assess the role of G(s alpha) on the whole-cell Ca2+ 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(s alpha)-nonexpressing littermates. The effect of G(s alpha) overexpression was mimicked by intracellular dialysis of wild-type cardiac myocytes with GTP gamma S-activated G(s alpha). 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(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 pathway and activation of endogenous adenylyl cyclase.