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.