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 IIB/IIX-->IIA-->I, the first step (IIB/IIX-->IIA) occurring after a short delay (2 weeks) and the last step (IIA-->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.

Figure 1. Long-term 20 Hz stimulation of denervated EDL muscle induces appearance of slow type I fibres

Cross-sections of EDL muscles that had been denervated plus stimulated for 124 days (A), denervated for 80 days (B), or was normal (C). The sections were stained with the BA-D5 antibody against type I MHC.

Figure 2. Denervated EDL contains mainly slow type I fibres after 4 months of 20 Hz stimulation

Serial cross-sections of an EDL muscle that had been denervated and stimulated for 124 days and then stained with antibodies against type I (A), IIA (B) and IIB (D) MHCs. The section in C was stained with the BF-35 antibody which reacts with types I, IIA, and IIB, but not IIX MHCs.

Figure 3. Transient appearance of type IIA fibres in denervated and 20 Hz stimulated EDL muscles

Cross-sections of EDL muscles after 10 (A), 43 (B), and 124 (C) days of denervation plus direct stimulation. The sections were stained with the BA-71 antibody against type IIA MHC.

Figure 4. Time course of changes in fibre types during 20 Hz stimulation of denervated EDL muscles

Percentage of different fibre types in EDL plotted against the length of time of denervation (^) or denervation plus direct stimulation (•). Each symbol represents one muscle. Curves fitted by eye are added.

Figure 5. Time course of changes in fibre types during 20 Hz stimulation of the nerve to EDL muscles

Percentage of different fibre types in innervated EDL muscles plotted against the length of time of stimulation through the peroneal nerve. The broken line is the same curve as in Fig. 4 and represents the effects of stimulating denervated EDL muscles.