title: Acetylcholine release in myasthenia gravis: regulation at single end-plate level.
abstract: 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 alpha-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 alpha-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.
authors.affiliation: Department of Physiology, University of Leiden, Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Plomp
authors.forename: G T
authors.initials: GT
authors.lastname: Van Kempen
authors.forename: M B
authors.initials: MB
authors.lastname: De Baets
authors.forename: Y M
authors.initials: YM
authors.lastname: Graus
authors.forename: J B
authors.initials: JB
authors.lastname: Kuks
authors.forename: P C
authors.initials: PC
authors.lastname: Molenaar
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000328:Adult; D000818:Animals; D004594:Electrophysiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009045:Motor Endplate / Q000503:physiopathology*; D009132:Muscles / Q000737:chemistry / Q000503:physiopathology; D009157:Myasthenia Gravis / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000032:analysis
chemical_list: D011950:Receptors, Cholinergic; D000109:Acetylcholine