Myasthenia gravis serum reduces acetylcholine sensitivity in cultured rat myotubes

Abstract

MYASTHENIA gravis is a neuromuscular disorder characterised by muscle weakness and fatigability. Muscle fibres from myasthenic patients have reduced amplitudes of endplate potentials and miniature endplate potentials^1,2. Early studies concluded that the disorder was presynaptic in origin because the postsynaptic chemosensitivity of the myasthenic muscle fibres was found to be normal¹, but recent evidence indicates that myasthenia gravis is an autoimmune disease directed against the postsynaptic acetylcholine receptors^3,4. Myasthenic serum globulin has been shown to bind to the acetylcholine receptors^5,6, myasthenic muscle contains only 11–30% of α-bungarotoxin binding sites compared with normal muscle⁷, and iontophoretic studies showed that the acetylcholine sensitivity of the postsynaptic region of myasthenic muscle was markedly reduced². But the failure of in vitro application of myasthenic serum to reduce the junctional or extrajunctional sensitivity of human, rat or frog muscle⁸ has raised doubt on the involvement of the serum factor in the disease. In this report we show that the acetylcholine sensitivity of cultured rat myotubes is greatly reduced by in vitro application of myasthenic serum.