Acetylcholine receptor synthesis rate and levels of receptor subunit messenger RNAs in chick muscle.

Levels of mRNAs specific for the alpha-, gamma- and delta-subunit of the nicotinic acetylcholine receptor were measured in chick skeletal muscle by solution hybridization, using a genomic DNA probe containing the intramembrane segments M2 and M3 of the alpha-subunit and probes comprising exons 2-6 and exons 4-8, respectively, of the gamma- and delta-subunit. In the innervated calf musculature of adult chickens, receptor-specific messages were detected in approx. 100-fold excess over the amount required to account for the observed synthesis rate. Within 1 week after section of the sciatic nerve, alpha-, gamma- and delta-subunit message levels rose 112-, 42- and 24-fold, respectively, while receptor expression rate increased about 150-fold. The rise in message levels preceded the denervation-induced increase in receptor concentration. In differentiating myogenic cells all three messages were found in excess over the amounts required for the observed rate of receptor synthesis. Treatment of differentiated myotubes with drugs that change receptor synthesis rate selectively affects alpha-subunit mRNA. In all situations in vitro and in vivo the alpha-subunit mRNA was found to reach final levels faster, and to be from 3 to over 30 times more abundant, than the other messages. These observations corroborate earlier evidence for a regulatory mechanism in which the supply of mRNA determines acetylcholine receptor synthesis rate. They also suggest that receptor expression is not simply proportional to acetylcholine receptor subunit mRNA concentrations, but rather is controlled, to a considerable extent, by the efficiency with which the receptor-specific mRNAs and/or the subunits they code for are subsequently utilized.