期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1998
卷号：95
期号：16
页码：9669-9674
DOI：10.1073/pnas.95.16.9669
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The subunit of the stimulatory heterotrimeric G protein (Gs) is critical for the {beta}-adrenergic receptor activation of the cAMP messenger system. The role of Gs in regulating cardiac Ca2+ channel activity, however, remains controversial. Cultured neonatal cardiac myocytes from transgenic mice overexpressing cardiac Gs were used to assess the role of Gs on the whole-cell Ca2+ currents (ICa). Cardiac myocytes from transgenic mice had a 490% higher peak ICa compared with those of either wild-type controls or Gs-nonexpressing littermates. The effect of Gs overexpression was mimicked by intracellular dialysis of wild-type cardiac myocytes with GTP{gamma}S-activated Gs. 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 Gs. The data indicate that Gs overexpression is associated with a constitutive enhancement of ICa which is independent of the cAMP pathway and activation of endogenous adenylyl cyclase.
