Changes in satellite cell content and myosin isoforms in low-frequency-stimulated fast muscle of hypothyroid rat

Chronic low-frequency stimulation was used to study the effects of enhanced contractile activity on satellite cell content and myosin isoform expression in extensor digitorum longus muscles from hypothyroid rats. As verified by immunohistochemical staining for desmin, vimentin, and myosin heavy chain (MHC) isoforms and by histological analysis, stimulation induced a transformation of existing fast fibers toward slower fibers without signs of fiber deterioration or regeneration. Immunohistochemically detected increases in MHC I and MHC IIa isoforms, as well as reduced numbers of fibers expressing the faster MHC isoforms, mirrored the rearrangement of the thick-filament composition. These changes, especially the upregulation of MHC IIa, were accompanied by an induction of developmental MHC isoforms in the transforming adult fibers. Satellite cell content rose 2.6-, 3.0-, and 3.7-fold over that of corresponding controls (P < 0.05 in all cases) in 5-, 10-, and 20-day-stimulated muscles, respectively. Hypothyroidism alone had no effect on satellite cell content but resulted in a significant reduction in fiber size. The relative satellite cell contents increased (P < 0.05) from 3.8% in euthyroid control muscles to 7.9, 11.5, and 13.8% in the 5-, 10-, and 20-day-stimulated hypothyroid muscles, respectively. In 20-day-stimulated muscles, the relative satellite cell content reached an almost twofold higher level than that of normal slow-twitch soleus muscle. This increase occurred concomitantly with a rise in myonuclear density, most probably because of the fusion of satellite cells with existing fibers.