Human myasthenic sera reduce acetylcholine sensitivity of human muscle cells in tissue culture

Abstract

MYASTHENIA gravis is a muscle disease of man characterised by impaired neuromuscular transmission during repetitive motor nerve activity. Recent studies suggest that the defect in myasthenia gravis is post-synaptic and that myasthenic end-plates have a lower density of functional acetylcholine (ACh) receptors than normal end-plates. Thus end-plates from myasthenic patients show unusually small miniature end-plate potentials^1,2, are less sensitive than normal end-plates to iontophoretically applied ACh (refs 2, 3) and bind reduced amounts of α-bungarotoxin^4,5—a snake neurotoxin which is considered to bind specifically to nicotinic ACh receptors (see ref. 5). The presence of antibodies against ACh receptors in the sera of myasthenic but not of control patients^6–10 suggests that anti-receptor antibodies might act in some way to decrease the number of functional receptors at the motor end-plate. Previous investigations, however, have failed to show conclusively that myasthenic sera contain a factor that reduces muscle ACh sensitivity^3,11–13. Here we show that myasthenic sera can reduce the ACh sensitivity of tissue cultured human muscle cells.