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


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 ( without inducing waning of contractilities or run-down of trains of 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 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 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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