Effect of sera from myasthenia gravis patients and of alpha-bungarotoxin on acetylcholinesterase during in vitro neuromuscular synaptogenesis.
Myasthenia gravis (MG) is mediated by circulating antibodies directed against acetylcholine receptor (AChR) but the antibody titre is poorly correlated with the clinical severity of the disease. We analysed acetylcholinesterase (AChE) activity, molecular forms and distribution during in vitro synaptogenesis, in the presence of sera from MG patient. We observed that the formation of AChE patches is inhibited in proportion to the anti-AChR antibody titre, whatever the clinical severity of the disease. The total activity and the proportion of the different molecular forms were unchanged suggesting that AChE level and distribution are controlled by independent mechanisms. To clarify the relationship between the mechanisms of AChE concentration during synaptogenesis and AChR concentration, we compared the effect of MG sera (receptors are internalised and degraded) and of the acetylcholine antagonist alpha-bungarotoxin (non-functional receptors are still present in the muscular membrane). In the presence of alpha-bungarotoxin, the number of AChR clusters, and AChE activity and concentration were equivalent to control values. The comparison of the results obtained with antibodies and alpha-bungarotoxin suggests that the presence and/or concentration of AChR is a necessary condition for normal concentration of AChE during synaptogenesis.
de la Porte
S
S
Laboratoire de Neurobiologie Cellulaire, CNRS URA 1126 Université Bordeaux II, Talence, France.
Ragueh
F
F
Eymard
B
B
Courbin
P
P
Chapron
J
J
Koenig
J
J
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000097:blood* / Q000276:immunology; D002038:Bungarotoxins / Q000494:pharmacology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D009132:Muscles / Q000166:cytology; D009157:Myasthenia Gravis / Q000097:blood* / Q000276:immunology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011950:Receptors, Cholinergic / Q000276:immunology*; D011978:Receptors, Nicotinic / Q000276:immunology / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D001323:Autoantibodies; D002038:Bungarotoxins; C579167:Chrna7 protein, human; C579165:Chrna7 protein, rat; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D000110:Acetylcholinesterase