Role for calcium from the sarcoplasmic reticulum in coupling muscle activity to nicotinic acetylcholine receptor gene expression in rat.
Neurally evoked muscle electrical activity suppresses nicotinic acetylcholine receptor (nAChR) gene expression in extrajunctional domains of adult muscle fibers. It has been proposed that this regulation is mediated by calcium influx through voltage-dependent L-type calcium channels but bypasses the sarcoplasmic reticulum in chick and mouse C2C12 cells. Here we report that in rat muscle calcium influx through L-type calcium channels preferentially reduced nAChR epsilon-subunit RNA via a post-transcriptional mechanism. In contrast, calcium release from the sarcoplasmic reticulum (SR) suppressed nAChR subunit RNA levels as a result of decreasing nAChR subunit promoter activity. Finally, we show that this decreased promoter activity is mediated through the same DNA sequences that control activity-dependent gene expression. Therefore, we propose that in rat muscle, calcium release from the SR participates in coupling muscle depolarization to nAChR gene expression.
Adams
L
L
Mental Health Research Institute and Department of Biological Chemistry, University of Michigan, Ann Arbor 48109, USA.
Goldman
D
D
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D002645:Chickens; D004247:DNA / Q000235:genetics / Q000502:physiology; D003620:Dantrolene / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000502:physiology*; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D009132:Muscles / Q000166:cytology / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011978:Receptors, Nicotinic / Q000235:genetics*; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
D009125:Muscle Relaxants, Central; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D012433:Ryanodine; D004247:DNA; D003620:Dantrolene; D002118:Calcium