FIBER-SPECIFIC REGULATION OF CA2-ATPASE ISOFORM EXPRESSION BY THYROID-HORMONE IN RAT SKELETAL-MUSCLE()

We studied the effect of thyroid hormone (3,5,3'-triiodo-L-thyronine, T-3) on the expression of sarcoplasmic reticulum (SR) fast- and slow-t ype Ca2+-ATPase isoforms, SERCA1 and SERCA2a, respectively, and total SR Ca2+-ATPase activity in rat skeletal muscle. Cross sections and hom ogenates of soleus and extensor digitorum longus muscles from hypo-, e u-, and hyperthyroid rats were examined, and expression of Ca2+-ATPase isoforms in individual fibers was compared with expression of fast (M HC II) and slow (MHC II) myosin heavy chain isoforms. In both muscles, T-3 induced a coordinated and full conversion to a fast-twitch phenot ype in one-half of the fibers that were slow twitch in the absence of T-3. The conversion was partial in the other one-half of the fibers, g iving rise to a mixed phenotype. The stimulation by T-3 of total SERCA expression in all fibers was reflected by increased SR Ca2+-ATPase ac tivity. The time course of the T-3-induced changes of SERCA isoform ex pression was examined 1-14 days after the start of daily T-3 treatment of euthyroid rats. SERCA1 expression was stimulated by T-3 at a pretr anslational level in all fibers. SERCA2a mRNA expression was transient ly stimulated and disappeared in a subset of fibers. In these fibers S R Ca2+-ATPase activity was high because of high SERCA1 protein levels. These data suggest that the ultimate downregulation of SERCA2a expres sion, which is always associated with high SR Ca2+-ATPase activities, occurs at a pretranslational level.