Regulation of cardiac L-type Ca2+ channel by coexpression of G(alpha s) in Xenopus oocytes.
Activation of G(alpha s) via beta-adrenergic receptors enhances the activity of cardiac voltage-dependent Ca2+ channels of the L-type, mainly via protein kinase A (PKA)-dependent phosphorylation. Contribution of a PKA-independent effect of G(alpha s) has been proposed but remains controversial. We demonstrate that, in Xenopus oocytes, antisense knockdown of endogenous G(alpha s) reduced, whereas coexpression of G(alpha s) enhanced, currents via expressed cardiac L-type channels, independently of the presence of the auxiliary subunits alpha2/delta or beta2A. Coexpression of G(alpha s) did not increase the amount of alpha1C protein in whole oocytes or in the plasma membrane (measured immunochemically). Activation of coexpressed beta2 adrenergic receptors did not cause a detectable enhancement of channel activity; rather, a small cAMP-dependent decrease was observed. We conclude that coexpression of G(alpha s), but not its acute activation via beta-adrenergic receptors, enhances the activity of the cardiac L-type Ca2+ channel via a PKA-independent effect on the alpha1C subunit.
Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.
Y
Y
Blumenstein
T
T
Ivanina
E
E
Shistik
E
E
Bossi
A
A
Peres
N
N
Dascal
D058666:Adrenergic beta-2 Receptor Agonists; D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020746:Calcium Channels, L-Type; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D004594:Electrophysiology; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D009154:Mutation; D009638:Norepinephrine / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000502:physiology; D013449:Sulfonamides; D014982:Xenopus laevis
D058666:Adrenergic beta-2 Receptor Agonists; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D007546:Isoquinolines; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D013449:Sulfonamides; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019205:GTP-Binding Protein alpha Subunits, Gs; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D009638:Norepinephrine