Effect of 4-aminopyridine on the postsynaptic action of polymyxin B

Abstract

Polymyxin B produces neuromuscular blockade by acting at pre- and postsynaptic sites. Its postsynaptic effect has been attributed either to blockade of open ionic channels or to the conversion of the end-plate receptor from a low to a high affinity state, i.e. to a state similar to the desensitized one caused by agonists. Since 4-aminopyridine inhibits agonist-induced end-plate receptor desensitization, we decided to investigate its effect on the postsynaptic action of polymyxin B. The experiments were carried out on the isolated rat diaphragm; miniature end-plate potentials (m.e.p.p.s) and carbachol-induced depolarization at the end-plate region were recorded with microelectrode techniques. Polymyxin B, 40 ω;g/ml reduced the amplitude of the m.e.p.p.s. and suppressed them in about 30 min. 4-Aminopyridine completely antagonized this effect. Neostigmine did not restore the m.e.p.p.s. suppressed by polymyxin B nor did 4-aminopyridine antagonize the effect of d-tubocurarine on these potentials. The carbachol-induced depolarization was blocked only partially by polymyxin B. 4-Aminopyridine B nearly completely antagonized this effect. The antagonistic effect of 4-aminopyridine on the postsynaptic action of polymyxin B favors the receptor desensitization' hypothesis.