Studies on Neurotrophic Regulation of Skeletal Muscle

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This chapter discusses a study in which a quantitative comparison was made of the influence of denervation and botulinum toxin (BoTX) poisoning on the development of time tetrodotoxin (TTX) resistant action potentials in rat muscle. The experiments were carried out on the extensor digitorum longus (EDL) muscle of adult male rats. Clostridium botulinum toxin type A was injected into the anterolateral region of the right hind leg superficial to the tibialis anterior and EDL muscles. Surgical denervation of the EDL muscle was performed under ether anaesthesia by sectioning the peroneal nerve at the knee. The results show that despite causing complete paralysis BoTX is less effective than surgical denervation in inducing denervatory changes in skeletal muscle. This suggests that the presence of the botulinum-poisoned nerve prevents the appearance of the full blown signs of denervation. Since the influence of the botulinum poisoned nerve is blocked by a-neurotoxin, the residual release of acetylcholine is thought to be responsible for this neurotrophic action. It is concluded that a great number of neurotrophic factors, among which is acetylcholine, suppress the appearance of denervatory changes in skeletal muscle. The relative importance of each neurotrophic influence vanes quantitatively but not qualitatively between species and muscles studied. It is suggested that neurotrophic influences act on a common target mechanism “second messenger” in the muscle cell that in turn regulates the appearance of the signs of denervation.

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