Dihydropyridine receptor gene expression is regulated by inhibitors of myogenesis and is relatively insensitive to denervation.
To evaluate developmental and physiological signals that may influence expression of the dihydropyridine-sensitive "slow" Ca2+ channel, we analyzed dihydropyridine receptor (DHPR) mRNA abundance in mouse skeletal muscle. Using synthetic oligonucleotide probes corresponding to the rabbit skeletal muscle DHPR, a 6.5 kb DHPR transcript was identified in postnatal skeletal muscle and differentiated C2 or BC3H1 myocytes, but not cardiac muscle or brain. DHPR gene expression was reversibly suppressed by 0.4 nM transforming growth factor beta-1 or by transfection with a mutant c-H-ras allele, nominal inhibitors of myogenesis that block the appearance of slow channels and DHPR. In contrast, both BC3H1 and C2 myocytes containing the activated ras vector expressed the gene encoding the nicotinic acetylcholine receptor delta subunit, demonstrating that not all muscle-specific genes are extinguished by ras. Denervation stimulated DHPR gene expression less than 0.6-fold, despite 8-fold upregulation of delta-subunit mRNA and reciprocal effects on the skeletal and cardiac alpha-actin genes. Thus, DHPR gene induction is prevented by inhibitors of other muscle-specific genes, whereas, at most, relatively small changes in DHPR mRNA abundance occur during adaptation to denervation.
Shih
H T
HT
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
Wathen
M S
MS
Marshall
H B
HB
Caffrey
J M
JM
Schneider
M D
MD
D000222:Adaptation, Physiological; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D005786:Gene Expression Regulation; D011905:Genes, ras; D066298:In Vitro Techniques; D051379:Mice; D008809:Mice, Inbred C3H; D009121:Muscle Denervation; D009132:Muscles / Q000187:drug effects / Q000502:physiology*; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis; D011978:Receptors, Nicotinic / Q000235:genetics*; D015533:Transcriptional Activation; D015291:Transforming Growth Factors / Q000494:pharmacology
D015220:Calcium Channels; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D015291:Transforming Growth Factors