Effects of Motor Innervation on the Chemical Sensitivity of Skeletal Muscle

Abstract

A description of the effects of reduced motor nerve activity on the chemical sensitivity of skeletal muscle was presented. When a muscle fiber was deprived of its innervation the ACh-sensitive region at the end plate increased in size until it ultimately covered the whole muscle surface. Results obtained in muscles treated with botulinum toxin demonstrated that it was primarily a lack of transmitter release and not nerve degeneration that was responsible for the increase in size of the chemosensitive area. Furthermore, studies of ACh-sensitivity in fetal and newborn rat muscle revealed that the muscle fibers prior to a functional innervation were sensitive to the drug along their whole length. These findings suggest that a skeletal muscle, at an early stage of innervation or when denervated, is uniformly sensitive to ACh on its entire surface. When functional innervation is established the chemically sensitive area decreases in size from the tendons towards the end plate and the decrease is initiated and modified by the release of the chemical transmitter from the motor nerve. Due to the electric core conductor properties an increase in the chemically sensitive surface of a muscle fiber renders it supersensitive to depolarizing drugs. The increase in chemical sensitivity produced by this mechanism is of such a magnitude that it can account for the supersensitivity of chronically denervated skeletal muscle. Following denervation a "true" supersensitivity of drug receptors is not observed. The conversion of the muscle membrane into an ACh-sensitive surface allows the drug to depolarize the entire length of a muscle fiber and thereby provides an explanation for the ACh-contractures in denervated muscles. It was shown that application of ACh or repetitive motor nerve stimulation reversibly reduces the chemical sensitivty of existing ACh-receptors. Results were obtained indicating that, during high-frequency stimulation of the motor nerve, receptor "desensitization" is probably a limiting factor for the rate at which impulses propagate across the neuromuscular junction. The mechanism of receptor "desensitization" is unknown but it may be related to the processes by which transmitter release from the motor nerve influences the size of the receptor surface.