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 ace tylcholinesterase (AChE) activity, molecular forms and distribution du ring in vitro synaptogenesis, in the presence of sera from MG patient. We observed that the formation of AChE patches is inhibited in propor tion to the anti-AChR antibody titre, whatever the clinical severity o f the disease. The total activity and the proportion of the different molecular forms were unchanged suggesting that AChE level and distribu tion are controlled by independent mechanisms. To clarify the relation ship between the mechanisms of AChE concentration during synaptogenesi s and AChR concentration, we compared the effect of MG sera (receptors are internalised and degraded) and of the acetylcholine antagonist al pha-bungarotoxin (non-functional receptors are still present in the mu scular 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 antibodie s and alpha-bungarotoxin suggests that the presence and/or concentrati on of AChR is a necessary condition for normal concentration of AChE d uring synaptogenesis.