A re-examination of curare action at the motor endplate

Recent evidence indicates that curare, in addition to its ‘competitive’ interference with endplate receptors, can block open ionic channels by a ‘non-competitive’ action on the activated acetylcholine-receptor complex. These findings called for further study of the kinetic behaviour of endplate channels and their modification by curare. Examining impulse-evoked endplate currents and acetylcholine-induced current fluctuations, it is found that the lifetime of the open channel is shortened by relatively high concentrations of curare (greater than 5 μM), an effect which shows up most strikingly at hyperpolarized levels of membrane potential (— 130 mV and above). No shortening of this kind is observed when a neuromuscular block of equal or greater intensity is produced by a dose of α-bungarotoxin. Two other neuromuscular blocking agents, gallamine and pancuronium are shown to have an action on channel kinetics which cannot be explained by competitive receptor binding, but conforms to the hypothesis of rapidly repeated blocking and unblocking of individual ion channels, which had been proposed originally to account for the endplate action of local anaesthetics.