alpha-Conotoxin GI produces tetanic fade at the rat neuromuscular junction.
The ability of the marine snail toxin, alpha-conotoxin GI, to produce blockade of singly evoked twitches and to produce tetanic and train-of-four fade has been determined in the isolated rat hemidiaphragm preparation. Results were compared to those obtained with a reversible (vecuronium) and an irreversible (alpha-bungarotoxin) nicotinic acetylcholine antagonist and have been interpreted in terms of relative effects on post- and prejunctional nicotinic acetylcholine receptors at the neuromuscular junction. alpha-Conotoxin GI (0.5-2 microM) produced a concentration-dependent, readily reversible, decrease in the peak amplitude of single twitches and 50 Hz tetani, and an increase in tetanic and train-of-four fade. alpha-Conotoxin GI was consistently 2-3-fold more potent than vecuronium with respect to all of the measured tension parameters. Both alpha-conotoxin GI and vecuronium were approximately 2-fold more potent in producing tetanic fade and in blocking tetanic contractions than in blocking single twitches. In contrast to both alpha-conotoxin GI and vecuronium, alpha-bungarotoxin (0.13 microM) reduced the peak amplitude of both single twitches and 50 Hz tetani to the same extent without the appearance of a large degree of tetanic or train-of-four fade. Based on a comparison of the in vitro time course of neuromuscular block and of the relative effects of vecuronium, alpha-conotoxin GI and alpha-bungarotoxin on twitches, tetani and trains-of-four, we conclude that alpha-conotoxin GI has both pre- and postjunctional activity at the neuromuscular junction. In this respect, alpha-conotoxin GI resembles the clinically used competitive neuromuscular blocking drugs rather than the irreversible snake alpha-neurotoxins.
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, U.K.
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Blount
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Johnson
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Prior
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Marshall
D000818:Animals; D002038:Bungarotoxins / Q000633:toxicity*; D020916:Conotoxins; D003964:Diaphragm / Q000294:innervation; D004305:Dose-Response Relationship, Drug; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009466:Neuromuscular Blocking Agents / Q000633:toxicity*; D009469:Neuromuscular Junction / Q000187:drug effects*; D010456:Peptides, Cyclic / Q000633:toxicity*; D010791:Phrenic Nerve; D051381:Rats; D011919:Rats, Inbred Strains; D014673:Vecuronium Bromide / Q000633:toxicity*
D002038:Bungarotoxins; D020916:Conotoxins; D009466:Neuromuscular Blocking Agents; D010456:Peptides, Cyclic; C029960:conotoxin GI; D014673:Vecuronium Bromide