Electrophysiological studies of neuromuscular transmission in hereditary ‘motor end‐plate disease’ of the mouse

Studies have been made on isolated nerve-muscle preparations from mice with hereditary ;motor end-plate disease'.2. Spontaneous fibrillation was observed in the isolated preparation.3. Muscles gave only a weak twitch or failed to contract in response to nerve stimulation. Direct stimulation of muscles caused a twitch response which had a slower time course than normal. Peripheral nerve conduction was normal.4. Intracellular recording from single muscle fibres showed that with longer survival of the animal an increasing proportion of fibres failed to show end-plate potentials or action potentials in response to nerve stimulation.5. Miniature end-plate potentials (m.e.p.p.s) were recorded in almost all muscle fibres including those in which neuromuscular transmission had failed. The frequency of m.e.p.p.s was greater than normal, was not increased by tetanic stimulation of the nerve but was increased by a raised external potassium concentration.6. Muscle fibres were supersensitive to acetylcholine.7. The results suggest that the muscular weakness in this disease is due to the failure of nerve action potentials to invade motor nerve terminals so that muscle fibres become ;functionally denervated'.