Cardiac Gsalpha overexpression enhances L-type calcium channels through an adenylyl cyclase independent pathway.
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.
Lader
A S
AS
Renal Unit, Massachusetts General Hospital East, Charlestown, MA 02129, USA.
Xiao
Y F
YF
Ishikawa
Y
Y
Cui
Y
Y
Vatner
D E
DE
Vatner
S F
SF
Homcy
C J
CJ
Cantiello
H F
HF
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D015220:Calcium Channels / Q000378:metabolism*; D020746:Calcium Channels, L-Type; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D015398:Signal Transduction
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019205:GTP-Binding Protein alpha Subunits, Gs; D000262:Adenylyl Cyclases