Pre- and postsynaptic effects of nicotine on the mouse phrenic nerve-diaphragm preparation.
Nicotine at less than or equal to 33 microM enhanced the single twitch response to indirect stimulation but potentiated the blocking effect of tubocurarine. Failure of tetanic contraction (tetanic fade) occurred on stimulation at 100 Hz. At 76 microM, nicotine induced a first phase rapid (10 min) inhibition of twitch response followed later (60-90 min) by a second phase complete block. Neostigmine partially restored the response at either phase of block whereas diaminopyridine completely antagonized the blockade. The end-plate was depolarized maximally by only 10-15 mV within 30 min with 43 microM nicotine. The depolarization was maintained but was antagonized by tubocurarine. The twitch response induced by direct stimulation was unchanged indicating no depolarization block ensued. The amplitudes of both EPP (0.7 Hz) and MEPP were markedly depressed in parallel indicating a curare-like postsynaptic inhibition without an effect on the release of transmitter. It is concluded that nicotine blocks the neuromuscular transmission by a dual mechanism by its partial agonist action. At higher frequencies of transmission, nicotine (greater than or equal to 22 microM) also produced a remarkable run-down of EPP just like other receptor antagonists suggesting that the nerve terminal acetylcholine receptors are not particularly sensitive to nicotine as those on the autonomic ganglia.
D015761:4-Aminopyridine / Q000031:analogs & derivatives*; D000077770:Amifampridine; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003964:Diaphragm; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000187:drug effects / Q000502:physiology*; D009388:Neostigmine / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology*; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology*; D013390:Succinylcholine / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D014403:Tubocurarine / Q000494:pharmacology
D000631:Aminopyridines; D009388:Neostigmine; D009538:Nicotine; D015761:4-Aminopyridine; D013390:Succinylcholine; D000077770:Amifampridine; D002118:Calcium; D014403:Tubocurarine