Ultrastructural studies on the acetylcholine receptor at motor end plates of normal and pathologic muscles.

The acetylcholine receptors at the mammalian motor end plate have been counted and their distribution there determined ultrastructurally. Electron microscope autoradiography applied to muscles labeled with alpha-(3H)bungarotoxin was used for this purpose. The receptors are distributed asymmetrically along the postsynaptic membrane, being concentrated at the fold crests-that portion nearest to the presynaptic membrane. The density of receptor sites at that region is estimated to be 20,000-25,000 per mum2 of membrane surface. This density holds for the several species and muscle types thus far examined and appears to be a constant parameter of the motor end plate. It determines the limit of responsiveness to acetylcholine. By contrast, the enzyme acetylcholinesterase is found to be distributed evenly over the folds and may reside in the intersynaptic matrix. When mouse diaphragm end plates from dystrophic animals or animals following 5-day denervation were similarly examined, no significant alterations in either the density or the distribution of the receptor sites were found. Similarly, dystrophic muscles in chickens possess an unaltered number of receptors at their end plates. A model is outlined to correlate receptor and cholinesterase concentrations with known aspects of transmitter release. These findings may have relevance to some of the electrophysiological abnormalities seen in myasthenia gravis.