Electrophysiology and electron-microscopy of rat neuromuscular junctions after nerve degeneration

Abstract (1) Intracellular micro-electrodes and electron-microscopy were used to study normal and denervated end-plates in rat diaphragm muscle fibres. (2) In normal muscles 84.5 to 100% of the micro-electrode insertions were sufficiently close to the neuromuscular junction to detect miniature end-plate potentials. The structure of the normal neuromuscular junction had the usual 3-cell arrangement: muscle with synaptic folds, axon and Schwann cell. (3) Within one day after section of the phrenic nerve, the axon disintegrated and miniature end-plate potentials ceased to occur. Subsequently, miniature potentials were not observed at denervated end-plates, except during the third week after denervation, at which time a low-frequency discharge was seen in eight out of 770 fibres. The miniature potentials at these end-plates resembled those at normal junctions, and were presumably also due to acetylcholine acting on the muscle membrane. (4) The synaptic folds remain for several months after denervation, and serve to identify electron-microscopically the denervated end-plate. After prolonged denervation ( 3 weeks), when miniature end-plate potentials were never observed, there was generally no cell overlying the synaptic folds. (5) During the first 3 weeks after denervation, a nucleated cell, presumably the Schwann cell, was in close contact with the muscle. ‘Schwann-muscle' contacts were observed in muscle without miniature end-plate potentials. (6) Electron microscopy of a portion of denervated muscle, which included a fibre with miniature potentials, showed that the fibre had extensive ‘Schwann-muscle’ contacts. (7) It is concluded that the Schwann cell is the source of the packages of acetylcholine which evoke miniature end-plate potentials in denervated muscle. Since the Schwann cell was in contact with muscle fibres without miniature potentials, it appears that the presence of the Schwann cell is a necessary, but not a sufficient, condition for the production of miniature potentials at denervated end-plates.