Altered gene expression in steroid-treated denervated muscle

In rats treated with high-dose corticosteroids, skeletal muscle that is den ervated in vivo (steroid-denervated) develops electrical inexcitability sim ilar to that seen in patients with acute quadriplegic myopathy. To determin e whether changes in muscle gene transcription might underlie inexcitabilit y of steroid-denervated muscle we performed RNase protection assays to quan titate adult (SkM1) and embryonic (SkM2) sodium channel isoforms and chlori de channel (CLC-1) mRNA levels in control, denervated, steroid-innervated, and steroid-denervated skeletal muscle. While SkM1 mRNA levels were relativ ely unaffected by denervation or steroid treatment, SkM2 mRNA levels were i ncreased by both. These effects were synergistic and high levels of SkM2 mR NA were expressed in denervated muscle exposed to corticosteroids. Skeletal muscle CLC-1 mRNA levels were decreased by denervation. To better understa nd the marked upregulation of SkM2 in steroid-denervated muscle we examined changes in myogenin and glucocorticoid receptor mRNA levels. However, chan ges in these mRNA levels cannot account for the upregulation of SkM2 in ste roid-denervated muscle. (C) 1999 Academic Press.