Coupling muscle electrical activity to gene expression via a cAMP-dependent second messenger system.
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.
Mental Health Research Institute, University of Michigan, Ann Arbor 48109.
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Chahine
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Baracchini
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Goldman
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D004558:Electric Stimulation; D004594:Electrophysiology; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D009121:Muscle Denervation; D009124:Muscle Proteins / Q000235:genetics; D009132:Muscles / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011978:Receptors, Nicotinic / Q000235:genetics*; D015290:Second Messenger Systems; D013779:Tetrodotoxin / Q000494:pharmacology
D009124:Muscle Proteins; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D013779:Tetrodotoxin; D000242:Cyclic AMP; D011494:Protein Kinases