Serum contains a potent factor that decreases beta-adrenergic receptor-stimulated L-type Ca2+ current in cardiac myocytes.
L-type Ca2+ current (ICa) was measured in cultured atrial myocytes from hearts of adult guinea-pigs using whole-cell voltage clamp. Potentiation of ICa induced by beta-adrenergic stimulation (isoprenaline 2.10(-7) M) could be completely antagonized by diluted sera (1:100 v/v). Half-maximal inhibition of beta-receptor-stimulated ICa occurred at about 1:1000. Basal ICa was not affected by serum. Atropine in a concentration (10(-6) M) that completely antagonized the anti-adrenergic effect of acetylcholine (ACh, 2.10(-6) M) did not interfere with the effect of serum. In cells dialysed with cyclic adenosine monophosphate (cAMP)-containing (10(-4) M) pipette solution, potentiated ICa was insensitive to both ACh and serum. Preincubation of the myocytes with pertussis toxin almost completely abolished the anti-adrenergic effects of both ACh and serum. The potency of serum was not reduced by dialysis. It is concluded that serum contains a factor which, like ACh, inhibits beta-receptor-stimulated adenylyl cyclase via Gi-protein.
Department of Cell Physiology, Ruhr University Bochum, Germany.
K
K
Banach
M
M
Bünemann
J
J
Hüser
L
L
Pott
D000109:Acetylcholine / Q000494:pharmacology; D037361:Adenylate Cyclase Toxin; D000818:Animals; D016275:Atrial Function; D001285:Atropine / Q000494:pharmacology; D001769:Blood; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D004553:Electric Conductivity; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D037342:Pertussis Toxin; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D015220:Calcium Channels; D011943:Receptors, Adrenergic, beta; D010566:Virulence Factors, Bordetella; D001285:Atropine; D000242:Cyclic AMP; D037342:Pertussis Toxin; D007545:Isoproterenol; D000109:Acetylcholine