Neuronal-type acetylcholine receptors and regulation of ?7 gene expression in vertebrate skeletal muscle

Abstract

Several neuronal nicotinic acetylcholine receptor (AChR) genes are expressed in chick skeletal muscle during development. One of the most abundantly expressed is alpha 7, which produces a protein capable of binding alpha-bungarotoxin and is physically distinct from muscle AChRs containing the alpha 1 gene product. We show here that the alpha 7-containing species in muscle is indistinguishable pharmacologically from alpha 7-containing AChRs in neurons. In addition, immunologic analysis with subunit-specific muscle antibodies shows that the alpha 7-containing species in muscle lacks the beta 1 and delta muscle AChR gene products as it does the alpha 1. RNase protection experiments measuring alpha 7 mRNA levels indicate that the alpha 1 and alpha 7 genes may, in part, be subject to similar kinds of regulation in the tissue. Surgical denervation of leg muscle in newly hatched chicks caused a small and transient increase in alpha 7 mRNA after 8 days, while alpha 1 transcripts underwent a large and sustained increase in number. Similarly, treating myotube cultures with tetrodotoxin caused a modest increase in alpha 7 transcript levels and a large increase in alpha 1. Calcitonin gene-related peptide (CGRP) increased both kinds of transcripts in myotube cultures equally as did treatment with 8-bromo-cyclic AMP; CGRP is thought to work via a cyclic AMP-dependent pathway in muscle. In at least one respect, however, alpha 7 expression in muscle differs qualitatively from that of alpha 1: AChR-inducing activity (ARIA) increased alpha 1 mRNA levels in culture while slightly depressing alpha 7 mRNA levels. The regulatory pattern of alpha 7 expression in muscle may combine features of both alpha 7 expression in neurons and alpha 1 expression in muscle.