Onset of chronotropic effects of nicotinic drugs and tyramine on the sinoatrial pacemaker in chick embryo heart: relationship to the development of autonomic neuroeffector transmission.
Spontaneous electrical activity, recorded extracellularly from the sinoatriial pacemaker region in the isolated chick embryo heart, was inhibited by nicotine (10(-5)M) on the 11th incubation day and thereafter. Blockade of the inhibitory effects of nicotine hexamethonium, tetroditoxin and atropine supported the conclusion that nicotine initiated propagated impulses in postganglionic cholinergic nerves and released acetylcholine to act on atropine-sensitive receptors on pacemaker cells. Dimethylphenylpiperazinium, like nicotine, inhibited the sinoatrial pacemaker. The onset of the inhibitory effect of nicotine occurred within 1 day of the appearance of cholinergic neuroeffector transmission. The acceleratory action of tyramine (2.9 X 10(-5)M) increased markedly on the 20th incubation day, that is, within 1 day of the appearance of adrenergic neuroeffector transmission. The positive chronotropic effects of tyramine were opposed by cocaine and by propranolol. Nicotine also evoked pacemaker acceleration that was observed on the 21st incubation day and thereafter. However, the sympathomimetic effect of nicotine required elevation (2 times normal) of the external Ca++ concentration. Ontogenetic and pharmacologic evidence support the conclusion that the drug-induced changes in pacemaker impulse frequency depended upon an interaction with autonomic nerves. The results are consistent with the hypothesis that the gap between morphologic innervation of the heart by autonomic nerves and the appearance of transmission is related, at least in part, to the amount of transmitter available for release.
D000367:Age Factors; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000254:growth & development*; D002118:Calcium / Q000494:pharmacology; D002642:Chick Embryo; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D005731:Ganglionic Stimulants / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D006584:Hexamethonium Compounds / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D012849:Sinoatrial Node / Q000187:drug effects*; D013268:Stimulation, Chemical; D009435:Synaptic Transmission / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology*
D005731:Ganglionic Stimulants; D006584:Hexamethonium Compounds; D013779:Tetrodotoxin; D004246:Dimethylphenylpiperazinium Iodide; D009538:Nicotine; D001285:Atropine; D002118:Calcium; D014439:Tyramine