Alterations in neuromuscular transmission in myasthenia gravis as determined by studies of drug action

Abstract

The injection of ACh was found to produce, in normal subjects and in patients with myasthenia gravis, transient stimulation of motor unit activity followed by prompt transient depression of induced potentials, attributable to the depolarizing action of ACh. In myasthenic patients this was followed by a period of transient potentiation of induced potentials. In both normal subjects and myasthenic patients there then ensued a late prolonged depression of induced potentials, attributable to choline released as a result of hydrolysis of ACh. This late depression has the properties of a depolarizing block in normal subjects and a competitive block in patients with myasthenia gravis. These observations indicate that the defect in neuromuscular transmission in myasthenia gravis may be due to a competitive (ACh inhibitory) block produced by choline released in a normal manner during neuromuscular transmission following hydrolysis of endogenous ACh. The injection of ACh was found to produce, in normal subjects and in patients with myasthenia gravis, transient stimulation of motor unit activity followed by prompt transient depression of induced potentials, attributable to the depolarizing action of ACh. In myasthenic patients this was followed by a period of transient potentiation of induced potentials. In both normal subjects and myasthenic patients there then ensued a late prolonged depression of induced potentials, attributable to choline released as a result of hydrolysis of ACh. This late depression has the properties of a depolarizing block in normal subjects and a competitive block in patients with myasthenia gravis. These observations indicate that the defect in neuromuscular transmission in myasthenia gravis may be due to a competitive (ACh inhibitory) block produced by choline released in a normal manner during neuromuscular transmission following hydrolysis of endogenous ACh.