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Acetylcholine release in myasthenia gravis: Regulation at single end‐plate level
Author(s) -
Plomp Jaap J.,
van Kempen Gertrudis TH. H.,
de Baets Marc BscH.,
Graus Yvo M. F.,
Kuks Jan B. M.,
Molenaar Peter C.
Publication year - 1995
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410370513
Subject(s) - myasthenia gravis , acetylcholine , acetylcholine receptor , neuromuscular junction , endocrinology , postsynaptic potential , autoantibody , medicine , chemistry , receptor , immunology , neuroscience , biology , antibody
In myasthenia gravis, loss of acetylcholine receptors at motor end‐plates is induced by antireceptor autoantibodies. At end‐plates in rats in which myasthenia gravis–like symptoms are induced by chronic treatment with α‐bungarotoxin, acetylcholine release is increased. Within muscles from such rats there is a strong correlation between the increase of acetylcholine release at an end‐plate and the loss of postsynaptic acetylcholine receptors, caused by the toxin. The question is whether upregulation of acetylcholine release is a clinically relevant compensatory mechanism in myasthenia gravis or only a feature of the animal model using α‐bungarotoxin. We investigated electrophysiologically 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 muscle, the mean quantal content was considerably increased compared with control levels. At each individual myasthenic end‐plate, the increase in 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 gravis, in which retrograde acting factors (i.e., from muscle fiber to nerve terminal) upregulate acetylcholine release.