title: Botulinum toxin blocks quantal but not non-quantal release of ACh at the neuromuscular junction.
abstract: Botulinum (BOT) toxin is known to block quantal acetylcholine (ACh) release at the neuromuscular junction but little is known about its effect on non-quantal ACh release. We have examined the effect of BOT on non-quantal ACh release directly using a variant of the electrophysiological technique described by Katz and Miledi. This method is based on the observation that non-quantally released ACh results in a small, continual depolarization of the postsynaptic membrane, after inhibition of cholinesterase. This depolarization can be revealed by suddenly blocking ACh receptors with a pulse of curare, resulting in an abrupt hyperpolarization, the amplitude of which is presumed to be proportional to the rate of non-quantal ACh release. BOT treatment resulted in a marked decrease in quantal ACh release as shown by miniature endplate potential (m.e.p.p.) frequencies (control 0.65 +/- 0.33 m.e.p.p.s/s; BOT 0.03 +/- 0.03 m.e.p.p.s/s). However, non-quantal ACh release measured by the curare induced hyperpolarization, was not significantly different in control and BOT treated diaphragms (control 1.01 +/- 0.09 mV: BOT 1.03 +/- 0.11 mV). Our results show that BOT does not block non-quantal ACh release at a time when it has a profound effect on spontaneous quantal ACh release. This suggests that quantal and non-quantal ACh release take place through different release mechanisms.
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology*; D005260:Female; D008564:Membrane Potentials / Q000187:drug effects; D009045:Motor Endplate / Q000187:drug effects; D009115:Muridae; D009469:Neuromuscular Junction / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D014403:Tubocurarine / Q000494:pharmacology
chemical_list: D001905:Botulinum Toxins; D000109:Acetylcholine; D014403:Tubocurarine