Acetylcholine receptor expression in primary cultures of embryonic chick myotubes--I. Discoordinate regulation of alpha-, gamma- and delta-subunit gene expression by calcitonin gene-related peptide and by muscle electrical activity.

The neuropeptide calcitonin gene-related peptide calcitonin gene-related peptide, and muscle electrical activity regulate in opposite directions the content of nicotinic acetylcholine receptor alpha-subunit mRNA in primary cultures of chick embryonic myotubes. Indeed, treating the cells with calcitonin gene-related peptide or blocking the spontaneous activity of muscle cells by tetrodotoxin (an inhibitor of sodium channels) increases, although to different levels, the content of acetylcholine receptor alpha-subunit mRNA [Fontaine B., Klarsfeld A. and Changeux J. P. (1987) J. Cell Biol. 105, 1337-1342; Klarsfeld A. and Changeux J. P. (1985) Proc. natn. Acad. Sci. U.S.A. 82, 4558-4562]. In this paper, we demonstrate that, under these in vitro culture conditions, calcitonin gene-related peptide (0.1 microM) and tetrodotoxin (0.5 microM) regulate to a smaller extent (no more than 2.5-fold above control) the levels of acetylcholine receptor gamma- and delta-subunit mRNAs. No effect of either compound on acetylcholine receptor biosynthesis was observed during the initial three days of culture. The response to calcitonin gene-related peptide was already maximal when the cells were treated between days three and four after plating (about 3-fold increase of the alpha-subunit mRNA level). The effect of tetrodotoxin resulted in a six-fold increase of the acetylcholine receptor alpha-subunit mRNA level in cells treated between days three and four, and still increased when the cells were exposed to tetrodotoxin through days six and eight (up to a maximum of 20-fold).(ABSTRACT TRUNCATED AT 250 WORDS)