NEUROTOXINS IN THE STUDY OF NEURAL REGULATION OF MEMBRANE-PROTEINS IN SKELETAL-MUSCLE

The discovery and purification of several neurotoxins, including alpha-bungarotoxin and tetrodotoxin has provided very high-affinity ligands which have proved to be central to the elucidation of the neural control of skeletal muscle membrane proteins and to the purification and characterization of the nicotinic acetylcholine receptor (AChR) and the Na+ channel, respectively. This review describes the use of neurotoxins for quantification and localization of receptors and ion channels in normal and denervated skeletal muscles with particular emphasis on the appropriateness of the muscle preparation and ligand used in the studies. It is now clear that the nerve controls the synthesis and spatial distribution of AChRs and Na+ channels by regulating gene expression in extrajunctional and subjunctional nuclei. The down-regulation of extrajunctional AChRs is primarily mediated by neuromuscular activity and the concentration of AChRs and Na+ channels in specific membrane domains at the neuromuscular junction is controlled by a number of neurotrophic substances at the neuromuscular junction. These include agrin, ARIA, and CGRP.