Acetylcholine-induced channels and transmitter release at human endplates

Abstract

MYASTHENIA gravis, a disease affecting the human neuromuscular junction, is thought to result from a postsynaptic defect, namely a reduction in the number of functional acetylcholine (ACh) receptors (reviewed in ref. 1). Thus at myasthenic end-plates the spontaneous miniature endplate potentials (m.e.p.ps) and impulse-evoked endplate potentials (e.p.ps) are reduced in amplitude². Furthermore, the diminished number of α-bungarotoxin binding sites^3,4 indicates a reduction in the number of ACh receptors in the postsynaptic membrane which leads to a reduced sensitivity to ACh⁵; and preliminary experiments with voltage noise (B. Katz, R. M. & J. Newsom-Davis, unpublished) suggested that the decrease in sensitivity does not involve changes in the characteristics of the channels. We have further examined the properties of channels opened by ACh at normal and myasthenic endplates as well as some characteristics of transmitter release in the two conditions. The experiments described here indicate that the single channel conductance and the mean channel life-time are similar in normal and myasthenic muscle membranes but that there are differences in the Ca-dependence of transmitter release from normal and myasthenic nerve terminals.