Regulation of muscle AChR alpha subunit gene expression by electrical activity: involvement of protein kinase C and Ca2+.
Using primary cultures of chicken myotubes, we investigated the involvement of protein kinase C and Ca2+ in the repression of nicotinic acetylcholine receptor (AChR) biosynthesis by electrical activity. Treatment with the Ca2+ channel blocker verapamil or the Na+ channel blocker tetrodotoxin increased alpha subunit mRNA levels 11.5- to 15-fold. The effect of tetrodotoxin was abolished in the presence of the Ca2+ ionophore A23187. Dantrolene, which blocks Ca2+ efflux from the sarcoplasmic reticulum, caused only a 1.7-fold increase in alpha subunit mRNA levels. Down regulation of protein kinase C by prolonged exposure to the phorbol ester TPA or inhibition of protein kinase C by staurosporine led to 8- to 10-fold increases in alpha subunit mRNA levels. Mature and precursor forms of AChR alpha subunit mRNA were found to vary in parallel throughout all of these treatments, suggesting that protein kinase C and Ca2+ ions may modulate AChR alpha subunit biosynthesis at the transcriptional level.
Klarsfeld
A
A
U. R. A. CNRS 0210, Département des Biotechnologies, Institut Pasteur, Paris, France.
Laufer
R
R
Fontaine
B
B
Devillers-Thiéry
A
A
Dubreuil
C
C
Changeux
J P
JP
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D003620:Dantrolene / Q000494:pharmacology; D005786:Gene Expression Regulation; D046911:Macromolecular Substances; D009132:Muscles / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011950:Receptors, Cholinergic / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014158:Transcription, Genetic; D014700:Verapamil / Q000494:pharmacology
D046911:Macromolecular Substances; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D000001:Calcimycin; D013779:Tetrodotoxin; D014700:Verapamil; D011493:Protein Kinase C; D003620:Dantrolene; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium