Abstract
Embryonic-type nicotinic acetylcholine receptor (nAChR) gene expression is regulated by muscle activity. The mechanism by which this activity is transduced to the genome is not known. We have addressed this issue by using a rat primary muscle cell culture system that mimics the in vivo effects of muscle activity on nAChR expression. We report here that the suppression of nAChR gene expression by muscle activity can be reversed by increasing intracellular cAMP levels. This effect is specific to the embryonic-type receptor genes. Electrically insensitive genes such as those encoding the adult-type nAChR epsilon-subunit and creatine kinase are not up-regulated by cAMP. In addition, muscle inactivity caused either by tetrodotoxin or denervation increases cAMP levels and protein kinase A activity, consistent with their proposed role in mediating nAChR gene expression. Finally, we report that this same mechanism appears to regulate other genes, such as those encoding the tetrodotoxin-insensitive sodium channel, MyoD, and myogenin which, like the nAChR, are regulated by muscle electrical activity. Based on these results it is proposed that muscle electrical activity is coupled to gene expression via a cAMP-dependent second messenger system.
Highlights
Embryonic-type nicotinic acetylcholine receptor researchers with an excellent system for characterizing thegene expressionis regulated by muscle activ- role electrical activity plays inregulating the expression of a ity
Based on these results it is proposed that muscle electrical activity is coupled togeneexpressionvia a CAMP-dependentsecond messenger system
Unlike that found in the chick system, we report that muscle electrical activity mediates itesffect on embryonic-type nAChR subunit gene expression through a CAMP-dependent second messenger system
Summary
Embryonic-type nicotinic acetylcholine receptor researchers with an excellent system for characterizing the (nAChR)gene expressionis regulated by muscle activ- role electrical activity plays inregulating the expression of a ity. Quantitation of this effect revealed a range between 3a.5-fold (myogenin) and over a 50-fold (nAChR a-subunit)difference in RNAlevels in stimulated comparewdith TTX-treated cells derived from cDNA e19-1-1 as described previously (Goldman et al, (Fig. 1B).
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