DIHYDROPYRIDINE RECEPTOR GENE-EXPRESSION IN SKELETAL-MUSCLE FROM MDX AND CONTROL MICE

The expression of isoform-specific dihydropyrine receptor-calcium chan nel (DHPR) alpha 1-subunit genes was investigated in mdx and control m ouse diaphragm (DIA) and tibialis anterior (TA). RNase protection assa ys were carried out with a rat DHPR cDNA probe specific for skeletal m uscle and a mouse DHPR cDNA probe specific for cardiac muscle. The lev el of expression of the gene encoding the cardiac DHPR was very weak i n TA muscle from both control and mdx mice. Compared to TA, DLA. expre ssed mRNA for the cardiac isoform at significantly higher levels, but mdx and control mouse DIA levels were similar to one another. In contr ast, mRNA expression levels for the DHPR skeletal muscle isoform were lower in control DIA than TA. However, there was a dramatic increase i n the expression for the DHPR skeletal muscle isoform in mdr DIA compa red with control DIA, reaching the TA expression level, whereas dystro phy did not affect TA expression. [H-3]-PN200-110 binding was used to further assess DIA DHPR expression at the protein level. The density o f binding sites for the probe was not significantly affected in DIA mu scles of mdr vs. control mice, but it was reduced in older mdx and con trol mice. The increase in DHPR mRNA levels without a consequent incre ase in DHPR protein expression could be secondary to possible enhanced protein degradation which occurs in mdx DIA. The altered DHPR express ion levels found here do not appear to be responsible for the severe d eficits in contractile function of the mdx DIA. (C) 1997 Elsevier Scie nce B.V.