A non-immunogenic myasthenia gravis model and its application in a study of transsynaptic regulation at the neuromuscular junction.
A non-immunological model for myasthenia gravis was developed in rats: 'toxin-induced myasthenia gravis'. Rats were injected once every 48 h with 3-5 micrograms alpha-bungarotoxin for periods of up to 5 weeks. This treatment caused weakness, especially of facial muscles. Respiration, however, was unaffected. Miniature endplate potentials and 125I-alpha-bungarotoxin binding in the extensor digitorum longus muscles were severely reduced. Acetylcholine release evoked by electrical and chemical (50 mM KCl) stimulation was higher in diaphragms from alpha-bungarotoxin-treated rats than in those from control animals. Histological investigation of the tibialis anterior muscle provided no evidence that the endplates were enlarged. It is concluded that the activity of acetylcholine receptors influences the rate of transmitter release in the neuromuscular junction and it is suggested that a transsynaptic regulation process may be active in myasthenia gravis. The present animal model for myasthenia gravis seems very suitable for studying such a regulation of transmitter release.
Molenaar
P C
PC
Department of Physiology, University of Leiden, The Netherlands.
Oen
B S
BS
Plomp
J J
JJ
Van Kempen
G T
GT
Jennekens
F G
FG
Hesselmans
L F
LF
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism / Q000494:pharmacology*; D018680:Cholinergic Antagonists; D007457:Iodine Radioisotopes; D008297:Male; D009045:Motor Endplate / Q000187:drug effects / Q000502:physiology; D009132:Muscles / Q000378:metabolism; D009157:Myasthenia Gravis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D009469:Neuromuscular Junction / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D014403:Tubocurarine / Q000494:pharmacology
D002038:Bungarotoxins; D018680:Cholinergic Antagonists; D007457:Iodine Radioisotopes; D011950:Receptors, Cholinergic; D000109:Acetylcholine; D014403:Tubocurarine