The action of polymyxin B at the frog neuromuscular junction.
1 The effects of polymyxin B at the neuromuscular junction of the frog were studied by conventional electrophysiological and voltage clamp techniques. 2 At a concentration of 2.5 micrograms/ml polymyxin B produced neuromuscular blockade in 10 to 15 min neuromuscular block was characterized by a depressed e.p.p. quantal content (28 plus or minus 7), which was similar to that determined from endplates exposed to 13 mM magnesium (23 plus or minus 3), and a low e.p.p. quantal size, which was similar to that determined from endplates exposed to 3 microM (+)-tubocurarine. 3 Polymyxin B (0.25 to 0.75 micrograms/ml) decreased mean miniature e.p.pl amplitude with little effect on frequency. At a concentration of 5 micrograms/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. 5 4-Aminopyridine (20 micrometers) antagonized the depressed e.p.p. quantal content produced by polymyxin B but did not alter the shortened e.p.c. duration. 6 It is concluded that polymyxin B decreases quantal release and produces some degree of postjunctional receptor blockade and a marked and persistent blockade of of acetylcholine activated channels. The latter action may explain the difficulty of reversal of polymyxin B-induced neuromuscular blockade and its non-competitive nature.
D000200:Action Potentials / Q000187:drug effects; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D066298:In Vitro Techniques; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism; D011112:Polymyxin B / Q000494:pharmacology*; D011113:Polymyxins / Q000494:pharmacology*; D011894:Rana pipiens
D000631:Aminopyridines; D009466:Neuromuscular Blocking Agents; D018377:Neurotransmitter Agents; D011113:Polymyxins; D011112:Polymyxin B