The density of acetylcholine receptors and their sensitivity in the postsynaptic membrane of muscle endplates

Abstract

In various skeletal muscles, the mean density of acetylcholine receptors in the muscle postsynaptic membrane is constant at about 8700 per mum(2), even though the overall size of an endplate ranged from 400 mum(2) to 1300 mum(2) in these muscles. This measurement was by electron microscope autoradiography of alpha-[(3)H]bungarotoxin binding sites; only one-half of these, however, appear to be true active centers of the acetylcholine receptor. The highest density of these receptors is on the juxtaneuronal regions of the postsynaptic membrane, and their density in the depths of the fold is less than one quarter of that at the tips. A maximum sensitivity to externally applied acetylcholine, about 3000-5000 mV/nC, is found in diverse types of endplates when truly focal recording is achieved. This acetylcholine sensitivity appears to be determined by the local density of receptors in the membrane, and not by their total number at the endplate. A quantal efficiency term is also disclosed. The maximal sensitivity per molecule obtainable by microiontophoresis of acetylcholine is 5-10% of that operative when a quantum reacts. When acetylcholine is released from a vesicle, in contrast to its application from outside, geometric factors are more favorable. Consideration of the local packing density, acetylcholine molecule numbers, and the current flow when one quantum of acetylcholine interacts at the membrane suggests that one, or possibly two, activated receptor active centers are linked to one open gate of the ionic conductance modulator.