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 ex-pression was reversibly suppressed by 0.4 nM transforming growth factor j%-1 or by transfection with a mutant c-H-ras allele, nominal inhibitors of myogenesis that block the appear-ance of slow channels and DHPR. In contrast, both BC3HI and C2 myocytes containing the activated ras vector expressed the gene encoding the nicotinic acetylcholine receptor subunit, demonstrating that not all muscle-specific genes are extin-guished by ras. Denervation stimulated DHPR gene expres-sion less than 0.6-fold, despite 8-fold upregulation of 5-subunit mRNA and reciprocal effects on the skeletal and cardiac a-actin genes. Thus, DHPR gene induction is prevented by inhib-itors of other muscle-specific genes, whereas, at most, rela-tively small changes in DHPR mRNA abundance occur during adaptation to denervation. (J. Clin. Invest. 1990. 85:781-789.) calcium channels * differentiation * MyoDI- oncogenes * skele-tal muscle transforming growth factor,8-