Fiber transformation and fiber replacement in chronically stimulated muscle

Chronic low-frequency stimulation (CLFS) of fast-twitch muscles induces fast-to-slow fiber-type transitions that differ in their extent in rat and rabbit. Fast-twitch muscle of the normal rat responds to CLFS with sequential transitions in myosin heavy chain (HC) expression in the order HCIIb --> HCIId --> HCIIa. However, in rabbit muscle the changes proceed beyond the state of HCIIa and include, as a final step, the expression of the slow myosin HCI. The time course for the transitions in myosin HC expression at both the messenger ribonucleic acid and protein levels suggests that fiber-type conversions occur asynchronously in a sequential manner. Thus type IIB fibers convert first to type IID fibers; these fibers then transform into type IIA fibers, which in rabbit muscle ultimately change into type I fibers. This sequence and the related changes in myosin isoforms point to different thresholds of the genes encoding the various fast and slow myosin HC isoforms. Although transformation of existing fast fibers into slower fibers is the major process that underlies the stimulation-induced fast-to-slow conversion, fiber replacement may also contribute. In rabbit muscle CLFS may cause metabolic exhaustion and subsequent deterioration in a fraction of the fast-twitch glycolytic fibers. For the most part these are replaced by satellite cell-derived, newly formed slow-twitch fibers.