Stimulant effects of muscarinic agonists in embryonic chick ventricular muscle. Are the effects mediated by protein kinase C?
Muscarinic agonists at high concentrations produce stimulant effects in the heart. We used the embryonic chick ventricle, in which muscarinic receptor activation markedly increases phosphoinositide (PI) breakdown, to investigate the possibility that receptor-induced PI metabolism mediates the stimulant effects. In preparations paced at 0.5 to 1 Hz, carbachol (CCh; 10(-6) to 10(-3) M) shifted the action potential plateau to more positive potentials and markedly prolonged the action potential duration (APD). These effects were not associated with a change in the resting potential, did not fade with time and could be obtained in the presence of propranolol (3 x 10(-7) M) or tetrodotoxin (10(-6) M). The same effects could be obtained with acetylcholine or oxotremorine (10(-4) M) and could be suppressed with atropine (0.9 x 10(-6) M). The sensitivity of the APD to muscarinic agonists was high during early embryonic stages and declined rapidly with age. At days 3 to 5, the APD was prolonged in the presence of CCh by greater than 80% of its control value. After day 12, CCh had no prolonging effect on the APD. In nonpaced preparations, the agonist depolarized the membrane and/or induced automaticity in quiescent preparations. When automaticity was present, spontaneously or after addition of Ba++, the frequency of the automatic activity was increased by the agonist. These effects on resting potential and automaticity were also less marked in older embryos. CCh (10(-6) to 10(-4) M) evoked an atropine-sensitive positive inotropic effect in paced ventricular tissues in the presence of propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)
Mubagwa
K
K
Department of Pharmacology, University of Connecticut Health Center, Farmington.
Vites
A M
AM
Pappano
A J
AJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002642:Chick Embryo; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D010277:Parasympathomimetics / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology*
D010277:Parasympathomimetics; D010716:Phosphatidylinositols; D002217:Carbachol; D011493:Protein Kinase C; D007545:Isoproterenol