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. 1984 Jun;351:275–297. doi: 10.1113/jphysiol.1984.sp015245

Pre-and post-junctional effects of tubocurarine and other nicotinic antagonists during repetitive stimulation in the rat.

A J Gibb, I G Marshall
PMCID: PMC1193117  PMID: 6747867

Abstract

The effects of tubocurarine and trimetaphan have been examined at voltage-clamped rat diaphragm neuromuscular junctions during (a) single and repetitive stimulation of the phrenic nerve in cut muscles and (b) repetitive ionophoretic application of acetylcholine (ACh). Tubocurarine (2.5 X 10(-7)-10(-6)M) produced a concentration-dependent reduction in the amplitude of neurally evoked end-plate currents (e.p.c.s). It also reduced their time constant of decay (tau e.p.c.) in a manner that was independent of membrane potential, and not markedly dependent on the tubocurarine concentration. Likewise the snake alpha-neurotoxin, erabutoxin b, reduced the e.p.c. amplitude and produced a voltage-independent shortening of tau e.p.c. Estimates of mean channel lifetime (tau noise) from ACh-induced e.p.c. fluctuations revealed that (a) tau noise was 46.4 +/- 3.7% shorter than tau e.p.c. measured at the same end-plate. At these same end-plates in the presence of tubocurarine (2.5 X 10(-7)M) tau e.p.c. was 32.6 +/- 1.0% shorter than the control tau e.p.c. but tubocurarine did not change tau noise, (b) trimetaphan (2.5 X 10(-5)-2 X 10(-4)M) produced a concentration-dependent and voltage-dependent reduction of tau e.p.c., and a concentration-dependent reduction of peak e.p.c. amplitude. Trimetaphan (2.5 X 10(-5)M) produced a 50% reduction of tau noise. (a) Both tubocurarine and trimetaphan produced concentration-dependent increases in the run-down of trains of neurally evoked e.p.c.s (50 Hz, 0.4 s). This effect did not vary with membrane potential in tubocurarine, but was voltage dependent when induced by trimetaphan. (b) Erabutoxin b reduced the e.p.c. amplitude but did not produce any increase in the run-down of trains of neurally evoked e.p.c.s. During 50 Hz repetitive ionophoretic application of ACh, tubocurarine (2.5 X 10(-7)M) reduced the amplitude of each current in the train without inducing any run-down of the current amplitudes. This effect was not dependent on the membrane potential. In contrast trimetaphan (2.5 X 10(-5)M) induced a voltage-dependent run-down of trains of ionophoretically evoked e.p.c.s. We conclude that tubocurarine and erabutoxin b reduce the e.p.c. amplitude by blocking the post-junctional ACh receptor. Tubocurarine produces tetanic rundown of e.p.c.s. by a prejunctional mechanism, whereas the effects of trimetaphan during single and repetitive stimulation are at least partly due to block of the open ion channel associated with the ACh receptor.

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Selected References

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