Details

Autor(en) / Beteiligte

• Lader, A S
• Xiao, Y F
• Ishikawa, Y
• Cui, Y
• Vatner, D E
• Vatner, S F
• Homcy, C J
• Cantiello, H F

Titel

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

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1998-08, Vol.95 (16), p.9669-9674

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

1998

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• The alpha subunit of the stimulatory heterotrimeric G protein (Gsalpha) is critical for the beta-adrenergic receptor activation of the cAMP messenger system. The role of Gsalpha in regulating cardiac Ca2+ channel activity, however, remains controversial. Cultured neonatal cardiac myocytes from transgenic mice overexpressing cardiac Gsalpha were used to assess the role of Gsalpha 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 Gsalpha-nonexpressing littermates. The effect of Gsalpha overexpression was mimicked by intracellular dialysis of wild-type cardiac myocytes with GTPgammaS-activated Gsalpha. 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 Gsalpha. The data indicate that Gsalpha overexpression is associated with a constitutive enhancement of ICa which is independent of the cAMP pathway and activation of endogenous adenylyl cyclase.