Neurotrophic regulation of prejunctional and postjunctional membrane at the mammalian motor endplate

Abstract

The trophic influence of nerve on muscle was investigated by studying the effect of transecting the sciatic nerve or its branches at various distances from the extensor digitorum longus and soleus muscles. If the rate at which the muscle responds to denervation were related to the level of nerve transection, a neurotrophic mechanism would have to be postulated, because the operation abolishes such non-neurotrophic factors as neuromuscular transmission and muscle activity. partial membrane depolarization of muscle fibers and spread of extrajunctional sensitivity to acetylcholine occurred much sooner when the nerve was transected near the muscle than when it was transected farther away. These changes preceded the disappearance of spontaneous miniature endplate potentials, thus indicating that quantal release of acetylcholine is not responsible for the maintenance of the resting potential or for the distribution of acetylcholine receptors in innervated muscle. An increase in spontaneous transmitter release was observed prior to the disappearance of miniature endplate potentials. This increase, which reflects a partial depolarization of the prejunctional nerve membrane, occurred sooner when the nerve was transected near the muscle than when it was cut farther away. We therefore conclude that both the prejunctional nerve membrane and the postjunctional muscle membrane are regulated by a neurohumoral, trophic mechanism.