Botulinum toxin prevents stimulus-induced backfiring produced by neostigmine in the mouse phrenic nerve-diaphragm.
The origin of motor nerve antidromic activity (backfiring) induced by anticholinesterase treatment was examined in the mouse phrenic nerve-hemidiaphragm preparation. Botulinum toxin was used to determine whether backfiring is due to (a) a direct effect of the cholinesterase inhibitor on the nerve terminal, or (b) an indirect effect via the prolongation of the action of acetylcholine. In previously untreated control preparations, neostigmine produced spontaneous and stimulus-induced antidromic activity in the phrenic nerve when rapidly introduced into the diaphragm via its vasculature. This activity could be reversibly blocked by d-tubocurarine and decamethonium, but not by atropine. Neostigmine-induced backfiring did not occur in preparations in which transmitter release was blocked with botulinum toxin. Infusion of a small bolus of a high concentration of acetylcholine following neostigmine treatment resulted in a short-term increase in the incidence of antidromic activity, followed by block, in both controls and botulinum toxin-treated preparations. It is concluded that transmitter release is necessary for the production of backfiring following cholinesterase inhibition since neostigmine alone does not elicit antidromic activity in botulinum toxin-treated preparations at concentrations which are effective in controls. Our results support the hypothesis that the effects of neostigmine on the motoneurone terminal are mediated by the prolonged action of acetylcholine that occurs with inhibition of acetylcholinesterase.
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D009388:Neostigmine / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000502:physiology*; D010791:Phrenic Nerve / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects
D009388:Neostigmine; D001905:Botulinum Toxins; D000109:Acetylcholine