ACETYLCHOLINE-RELEASE IN MYASTHENIA-GRAVIS - REGULATION AT SINGLE END-PLATE LEVEL

In myasthenia gravis, loss of acetylcholine receptors at motor end-pla tes is induced by antireceptor autoantibodies. At end-plates in rats i n which myasthenia gravis-like symptoms are induced by chronic treatme nt with alpha-bungarotoxin, acetylcholine release is increased. Within muscles from such rats there is a strong correlation between the incr ease of acetylcholine release at an end-plate and the loss of postsyna ptic acetylcholine receptors, caused by the toxin. The question is whe ther upregulation of acetylcholine release is a clinically relevant co mpensatory mechanism in myasthenia gravis or only a feature of the ani mal model using alpha-bungarotoxin. We investigated electrophysiologic ally the in vitro acetylcholine release at end-plates of muscles from patients with myasthenia gravis and rats with experimental autoimmune myasthenia gravis where acetylcholine receptor reduction is caused by autoantibody attack. In both human and rat autoimmune myasthenic muscl e, the mean quantal content was considerably increased compared with c ontrol levels. At each individual myasthenic end-plate, the increase i n quantal content appeared to be correlated with the reduction of the amplitude of the miniature end-plate potential. This finding suggests the existence of an important compensatory mechanism in myasthenia gra vis, in which retrograde acting factors (i.e., from muscle fiber to ne rve terminal) upregulate acetylcholine release.