NEURONAL-TYPE ACETYLCHOLINE-RECEPTORS AND REGULATION OF ALPHA-7 GENE-EXPRESSION IN VERTEBRATE SKELETAL-MUSCLE

Several neuronal nicotinic acetylcholine receptor (AChR) genes are exp ressed in chick skeletal muscle during development. One of the most ab undantly expressed is alpha 7, which produces a protein capable of bin ding alpha-bungarotoxin and is physically distinct from muscle AChRs c ontaining the alpha 1 gene product. We show here that the alpha 7-cont aining species in muscle is indistinguishable pharmacologically from a lpha 7-containing AChRs in neurons. In addition, immunologic analysis with subunit-specific muscle antibodies shows that the alpha 7-contain ing species in muscle lacks the beta 1 and delta muscle AChR gene prod ucts as it does the alpha 1. RNase protection experiments measuring al pha 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. Surgica l denervation of leg muscle in newly hatched chicks caused a small and transient increase in alpha 7 mRNA after 8 days, while alpha 1 transc ripts underwent a large and sustained increase in number. Similarly, t reating 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 my otube 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 qual itatively from that of alpha 1: AChR-inducing activity (ARIA) increase d alpha 1 mRNA levels in culture while slightly depressing alpha 7 mRN A levers. The regulatory pattern of alpha 7 expression in muscle may c ombine features of both alpha 7 expression in neurons and alpha 1 expr ession in muscle. (C) 1997 John Wiley & Sons, Inc.