Membrane-delimited stimulation of heart cell calcium current by beta-adrenergic signal-transducing Gs protein.
A severalfold increase in calcium current (ICa) is a signal feature of the maximal beta-adrenergic response of the heart. It is generally ascribed to enhanced adenosine 3',5'-cyclic monophosphate (cAMP)-dependent phosphorylation of calcium (Ca) channels after beta-receptor activation of the guanosine nucleotide-binding (G) protein Gs, and Gs activation of the adenylyl cyclase cascade. We blocked phosphorylation pathways in guinea pig cardiomyocytes to unmask other possible ICa-stimulatory modes. In blocked cells, ICa increased by approximately 50% during 1) beta-receptor activation of Gs, 2) intracellular activation of Gs, and 3) intracellular application of preactivated Gs, We conclude that fast, membrane-delimited Gs modulation participates in the physiological regulation of cardiac ICa.
Pelzer
S
S
II. Physiologisches Institut, Medizinische Fakultät Universität des Saarlandes, Homburg/Saar, Federal Republic of Germany.
Shuba
Y M
YM
Asai
T
T
Codina
J
J
Birnbaumer
L
L
McDonald
T F
TF
Pelzer
D
D
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000493:pharmacokinetics*; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D000242:Cyclic AMP / Q000502:physiology; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation; D015290:Second Messenger Systems / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D000242:Cyclic AMP; D002118:Calcium