The action of polymyxin B at the frog neuromuscular juntion

The effects of polymyxin B at the neuromuscular junction of the frog were studied by conventional electrophysiological and voltage clamp techniques. At a concentration of 2.5 μg/ml polymyxin B produced neuromuscular blockade in 10 to 15 min and endplate potentials (e.p.ps) could be recorded. Resting membrane potential was unaffected. The neuromuscular block was characterized by a depressed e.p.p. quantal content (28 ± 7), which was similar to that determined from endplates exposed to 13 mm magnesium (23 ± 3), and a low e.p.p. quantal size, which was similar to that determined from endplates exposed to 3 μm (+)‐tubocurarine. Polymyxin B (0.25 to 0.75 μg/ml) decreased mean miniature e.p.p. amplitude with little effect on frequency. At a concentration of 5 μg/ml polymyxin B markedly shortened the duration of endplate currents (e.p.cs) and abolished the relationship between holding potential and the time to half‐decay at negative potentials greater than −;60 mV. This action is consistent with block of open acetylcholine activated ionic channels. 4‐Aminopyridine (20 μm) antagonized the depressed e.p.p. quantal content produced by polymyxin B but did not alter the shortened e.p.c. duration. It is concluded that polymyxin B decreases quantal release and produces some degree of postjunctional receptor blockade and a marked and persistent blockade of acetylcholine activated channels. The latter action may explain the difficulty of reversal of polymyxin B‐induced neuromuscular blockade and its non‐competitive nature. 1981 British Pharmacological Society