Fast to slow transformation of denervated and electrically stimulated rat muscle

Abstract

1. Denervated fast extensor digitorum longus (EDL) muscles of adult rats were stimulated electrically for up to 4 months with a 'slow' pattern resembling the activity in soleus (Sol) motor units and examined with antibodies against myosin heavy chains (MHCs). 2. The normal EDL contained, on average, 45% type IIB, 29% type IIX, 23% type IIA and 3% type I fibres. All type IIB and almost all type IIX fibres disappeared during the first 3 weeks of stimulation. They were replaced by type IIA and type I fibres, whose percentages increased to about 75 and 15, respectively. Type IIA fibres remained at 75% for nearly 2 months and were then gradually replaced by type I fibres during the next 2 months. The transformation occurred sequentially in the order II BÏII X II A I, the first step (II BÏII X II A) occurring after a short delay (2 weeks) and the last step (II A I in originally IIB or IIX fibres) after a long delay (> 2 months). During the transformation coexpression of MHCs occurred. 3. It appears that the transformation to type I fibres occurred in pre-existing type II fibres since no signs of fibre damage or regeneration were observed. 4. Normal EDL was also stimulated through an intact nerve with the same pattern for up to 37 days. The effects on fibre type distributions were identical to those observed in the denervated EDL. The result indicated that the Sol-like pattern of evoked muscle activity, rather than nerve-derived trophic influences or denervation per se, was primarily responsible for the fast to slow transformation.

Denervation produces different single fiber phenotypes in fast- and slow-twitch hindlimb muscles of the rat

“…Thus, the pattern of fiber transformation upon denervation differs not only between EDL and SOL muscles from the same rat, but also between EDL muscles of different rat strains that have a different fiber type composition before denervation. The pattern of denervation-induced changes in MHC isoform composition in the EDL muscles nevertheless follows the general pattern of denervation-induced changes in MHC composition for fast-twitch muscles: from faster to slower MHC isoforms (34), although it appears from this study and others (13,17,47) that denervated EDL muscle does not express new MHC isoforms that were not expressed in the muscle before denervation.…”

“…In Wistar rats, denervation of the EDL muscle results in fiber transformation such that ϳ75% of fibers are of type IIA at day 60 post denervation, rising to ϳ90% by day 130 post-denervation (47). Thus, the pattern of fiber transformation upon denervation differs not only between EDL and SOL muscles from the same rat, but also between EDL muscles of different rat strains that have a different fiber type composition before denervation.…”

“…In Wistar-Kyoto rats, the EDL muscles contain in addition to the predominant IIb and IId MHC isoforms/type IIB and type IID fibers, 8 -20% IIa MHC/IIA fibers, and small amounts of MHCI/ type I fibers (13,17,47). In a previous study (2), we also found that type IIA and IIA/IID hybrid fibers were present in sizeable proportions in both EDL (9.6 and 17.3%) and SOL (7.5 and 8.2%) muscles of Wistar-Kyoto rats.…”

Specification of Optic Nerve Oligodendrocyte Precursors by Retinal Ganglion Cell Axons

“…In Drosophila the growth of optic axons to the brain stimulates neurogenesis in the visual centers (Huang and Kunes, 1996). In the periphery the acquisition of fast or slow muscle phenotype is modulated by the nature of the innervating neurons (Windisch et al, 1998), whereas innervation of skeletal muscle results in multiple molecular responses, including clustering of acetylcholine receptors and assembly of the postsynaptic machinery (Role et al, 1985;McMahan, 1990;Gautam et al, 1996).…”

Atrophy, but not necrosis, in rabbit skeletal muscle denervated for periods up to one year

“…Initially, fast (type II) fibers are more susceptible to atrophy than slow (type I) fibers (5,7,32,38,48,54,59), but over more prolonged periods the fiber types atrophy to a similar extent (6, 54). Corresponding to this reduction in fiber CSA, there is a striking and progressive increase in interstitial collagen and fat (32).…”