Untitled

Abstract

Chronic low-frequency stimulation (CLFS) of rat fast-twitch muscles induces sequential transitions in myosin heavy chain (MHC) expression from MHCIIb --> MHCIId/x --> MHCIIa. However, the 'final' step of the fast-to-slow transition, i.e., the upregulation of MHCI, has been observed only after extremely long stimulation periods. Assuming that fibre degeneration/regeneration might be involved in the upregulation of slow myosin, we investigated the effects of CLFS on extensor digitorum longus (EDL) muscles regenerating after bupivacaine-induced fibre necrosis. Normal, non-regenerating muscles responded to both 30- and 60-day CLFS with fast MHC isoform transitions (MHCIIb --> MHCIId --> MHCIIa) and only slight increases in MHCI. CLFS of regenerating EDL muscles caused similar transitions among the fast isoforms but, in addition, caused significant increases in MHCI (to approximately 30% relative concentration). Stimulation periods of 30 and 60 days induced similar changes in the regenerating bupivacaine-treated muscles, indicating that the upregulation of slow myosin was restricted to regenerating fibres, but only during an early stage of regeneration. These results suggest that satellite cells and/or regenerating fast rat muscle fibres are capable of switching directly to a slow program under the influence of CLFS and, therefore, appear to be more malleable than adult fibres.

NFAT is a nerve activity sensor in skeletal muscle and controls activity-dependent myosin switching

“…In contrast, a significant increase in MyHC-slow is induced after stimulation of the regenerating EDL muscle (ref. 33 and our unpublished observations), reflecting a greater plasticity of regenerating compared to mature muscle, as observed in other experimental settings (34,35). Interestingly, a MyHC-slow promoter-reporter construct is up-regulated by caNFATc1 in both regenerating and adult fast muscles.…”

Knee Extensors Muscle Plasticity Over a 5-Years Rehabilitation Process After Open Knee Surgery

“…An important aspect of our study was that we identified that the slow-to-fast fiber transition of muscle fiber types in knee extensor muscle was reversible ( Figure 2 ). Apart from investigations with disused muscle in laboratory species ( Desplanches et al, 1987 ; Pette et al, 2002 ), the former phenomenon has to the best of our knowledge only been described in one human study with 12-weeks of strength training of young subjects after 3 weeks of immobilization ( Howald, 1982 ; Hortobagyi et al, 2000 ; Fluck and Hoppeler, 2003 ; Wilson et al, 2012 ). Our findings now indicate that the reestablishment of the normal fiber type distribution in ACL-insufficient patients in the physiological context of standard rehabilitation and self-motivated exercise may take years to complete.…”

“…These alterations may be accompanied by the rarefaction of capillaries ( Adair and Montani, 2010 ), and collectively reduce aerobic capacity and the capacity for force production ( Desplanches et al, 1987 ; Pette, 2001 ). Increasing contractile activity subsequent to disuse elevates the metabolic capacity of skeletal muscle by enhancing the volume content or density of mitochondria and capillaries, and capillary-to-fiber ratio, and reestablishes the normal distribution and cross sectional area of muscle fiber types [reviewed in ( Desplanches et al, 1987 ; Pette et al, 2002 ; Fluck and Hoppeler, 2003 )]. In a single example with young subjects it has been shown that slow-to-fast transformation also occurs in knee extensor muscle of human subjects with durations of immobilization as short as 3 weeks and can be reversed by subsequent strength training over a period of 12 weeks ( Hortobagyi et al, 2000 ).…”

Enhanced exercise and regenerative capacity in a mouse model that violates size constraints of oxidative muscle fibres

“…However, these studies never examined whether Type I were formed as a consequence of the remodeling of Type II fibres or through the formation of new fibres, a process that would require satellite cells. Indeed the development of Type I fibres following extended CLFS can only be induced to significant levels when accompanied by robust myofibre regeneration ( Pette et al, 2002 ; Maier et al, 1988 ). Taken together, these studies imply that myostatin signalling acts at an embryonic/foetal stage of muscle development to pattern a subpopulation of satellite cells/muscle precursors in a muscle specific manner to form Type I fibres.…”