Calcium-dependent regulation of rat and chick muscle nicotinic acetylcholine receptor (nAChR) gene expression.
Muscle depolarization leads to decreased expression of nicotinic acetylcholine receptor (nAChR) genes in extrajunctional regions of the muscle fiber with little effect on their expression at the neuromuscular junction (NMJ). Depolarization-dependent decreases in nAChR gene expression have been linked to a cAMP-dependent signaling system in rat (Chahine, K. G., Baracchini, E., and Goldman, D. (1993) J. Biol. Chem. 2893-2898), and a calcium-dependent protein kinase C (PKC) signaling system in chick (Klarsfeld, A., Laufer, R., Fontaine, B., Devillers-Thiery, A., Bubreuil, C., and Changeux, J. P. (1989) Neuron 2, 1229-1236). We report here on experiments investigating the role of calcium and PKC in regulating rat muscle nAChR gene expression. These studies indicate that depolarization-dependent regulation of rat muscle nAChR gene expression is independent of PKC activity. However, these genes are regulated by a calcium-dependent signal transduction system. Calcium influx across the plasma membrane decreases nAChR gene expression in inactive rat myotubes. Surprisingly, this influx of extracellular calcium is most effective at reducing nAChR epsilon-subunit gene expression. We also provide evidence that a similar signal transduction system is capable of regulating nAChR gene expression in chick muscle. Based on these data we propose that calcium, in addition to mediating depolarization-dependent regulation of nAChR expression, may also participate in restricting their expression to the neuromuscular junctions of adult muscle fibers.
Department of Biological Chemistry, University of Michigan, Ann Arbor 48109.
W
W
Walke
J
J
Staple
L
L
Adams
M
M
Gnegy
K
K
Chahine
D
D
Goldman
D000818:Animals; D001483:Base Sequence; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002478:Cells, Cultured; D002642:Chick Embryo; D005786:Gene Expression Regulation / Q000187:drug effects*; D008969:Molecular Sequence Data; D024510:Muscle Development; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011978:Receptors, Nicotinic / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014018:Tissue Distribution; D014158:Transcription, Genetic
D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; D000001:Calcimycin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium