Distribution of calcitonin gene-related peptide at the neuromuscular junction of mdx mice.

Abstract

In normal skeletal muscle, the protein dystrophin is associated with plasma membrane glycoproteins and may be involved in the stabilization of the sarcolemma. Mutant mdx mice are markedly deficient in dystrophin and show muscle fiber necrosis followed by regeneration. Changes in the distribution of acetylcholine receptors (AChRs) have been reported at the neuromuscular junction of mdx mice possibly as a result of alterations in the release or response to neural trophic factors. One such factor is calcitonin gene-related peptide (CGRP), which has been implicated in AChR synthesis and function. In this study, we used rhodamine-alpha-bungarotoxin and anti-CGRP IgG FITC to study AChR and CGRP distribution at the neuromuscular junction of mdx mice. Using laser scanning fluorescence confocal microscopy, it was possible to see that CGRP-like immunoreactivity had a presynaptic distribution, covering the AChRs. Thirty-four percent of dystrophic junctions were found to be labeled with CGRP compared to 80% of control endplates. Since CGRP-positive and -negative fibers showed similar changes in AChR distribution, it is suggested that CGRP is probably not directly involved in the altered pattern of AChR seen in dystrophin-deficient muscle fibers of mdx mice.