Electrical events associated with the action of nicotine at the adrenergic nerve terminal.
Nicotine perfused through the coronary circulation of the isolated atropinized cat heart elicits antidromic activity in the cardiac sympathetic nerves. The pattern of discharge varies in a complex fashion with dose. At low concentrations, activity may last up to 10 min, whereas at high doses the antidromic response may last only a few seconds. Sympathetic transmitter is released into the perfusion fluid. There is dissociation between the amount of transmitter that overflows from the heart and the total antidromic activity with increasing dose of nicotine. With smaller doses of nicotine, the magnitude of the antidromic activity probably indicates the level of depolarization of the nerve terminal. Injection of greater doses of nicotine causes still greater transmitter release but not the generation of antidromic impulses, due presumably to persistent depolarization below a critical level. During the nicotine infusion and immediately afterwards, the antidromic response to acetylcholine and the effector responses associated with the adrenergic transmitter release by acetylcholine and sympathetic nerve stimulation were blocked. The rates of recovery of these responses were similar with a half-time of 4 to 5 min. Although the antidromic response to KCl was blocked during the nicotine infusion, it recovered more rapidly. Within 1-1.5 min, the antidromic response to KCl tended to exceed control levels. It is proposed that nicotine causes a prolonged depolarization of the membrane of the adrenergic nerve terminal. The site of action of nicotine, the basis of its prolonged action, and the interrelationship of this depolarization with transmitter release and intracellular uptake are discussed.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002415:Cats; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009411:Nerve Endings / Q000187:drug effects* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D013997:Time Factors
D018377:Neurotransmitter Agents; D011189:Potassium Chloride; D009538:Nicotine; D000109:Acetylcholine