title: The positive chronotropic effect of acetylcholine has muscarinic and nicotinic components in the neonatal rat heart.
abstract: Acetylcholine increases ventricular automaticity in neonatal but not adult canine Purkinje fibers. In this study, we used a rat model to investigate the mechanism for the increased automaticity, and used surface electrodes to record spontaneous rates from the ventricular septa of three different age groups: 1 to 2 days old (neonates), 6 to 9 days old (1 week old) and adults. Acetylcholine, 10(-12) and 10(-11) M, induced a significant increase in automaticity from a control of 103 +/- 6.5 beats per min to 117 +/- 9.0 and 118 +/- 10.8 beats per min, respectively, in the neonates (P less than .05). The increase was attenuated by atropine, 2 x 10(-6) M (P = .05), and eliminated by propranolol, 2 x 10(-7) M, or hexamethonium, 5 x 10(-6) M (P less than .05). In 1-week-old rats, acetylcholine, 10(-12) M, induced a lesser increase in automaticity from a control of 106 +/- 13.0 to 113 +/- 14.0 beats per min (P less than .05). The increase was blocked by atropine, 2 x 10(-6) M, propranolol, 2 x 10(-7) M, and by hexamethonium, 5 x 10(-6) M (all P less than .05). In adults, acetylcholine did not increase automaticity. Among the neonatal septa, 82% showed increased automaticity with acetylcholine alone, 78% showed increased automaticity in the presence of atropine and 13% showed increased automaticity in the presence of either propranolol or hexamethonium, suggesting a largely nicotinic mediated and catecholamine dependent component. In 1-week-old septa, 75% showed increased automaticity with acetylcholine alone.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, Columbia University College of Physicians & Surgeons, New York, New York.
authors.forename: L S
authors.initials: LS
authors.lastname: Sun
authors.forename: L A
authors.initials: LA
authors.lastname: Roberts
authors.forename: M R
authors.initials: MR
authors.lastname: Rosen
authors.forename: R B
authors.initials: RB
authors.lastname: Robinson
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001285:Atropine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D006584:Hexamethonium Compounds / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013268:Stimulation, Chemical; D014439:Tyramine / Q000494:pharmacology
chemical_list: D006584:Hexamethonium Compounds; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D001285:Atropine; D011433:Propranolol; D000109:Acetylcholine; D014439:Tyramine