Run-down of neuromuscular transmission during repetitive nerve activity by nicotinic antagonists is not due to desensitization of the postsynaptic receptor

British Journal of Pharmacology
S J Hong, C C Chang

Abstract

1. Whether the function of the postsynaptic acetylcholine receptor is use-dependently affected by repetitive nerve stimulation in the presence of competitive antagonists was studied in the mouse phrenic nerve-hemidiaphragm preparation. 2. For electrophysiological experiments, the preparation was immobilized by synthetic mu-conotoxin, which preferentially blocks muscular Na-channels causing neither depolarization of the membrane potential, inhibition of quantal transmitter release, nor depression of nicotinic receptor function. 3. High concentrations of cobratoxin depressed indirect twitches and endplate potentials (e.p.ps) without inducing waning of contractilities or run-down of trains of e.p.ps evoked at 10-100 Hz. However, waning and run-down were accelerated after washout of the toxin despite diminished postsynaptic receptor blockade. Once the run-down of e.p.ps was produced by washout or low concentrations of cobratoxin, further depression of e.p.p. amplitude with high concentrations of cobratoxin did not attenuate the e.p.p. run-down. 4. The degrees of waning of tetanus and trains of e.p.ps produced by a very high concentration of tubocurarine (20 microM) were also less than that caused at a 100 fold lower concentration, ...Continue Reading

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Mu conotoxin GIIIC
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