Bigard, Xavier A., Chantal Janmot, Danièle Merino, Françoise Lienhard, Yannick C. Guezennec, and Anne D'Albis. Endurance training affects myosin heavy chain phenotype in regenerating fast-twitch muscle. J. Appl. Physiol. 81(6): 2658-2665, 1996.The aim of this study was to analyze the effects of treadmill training (2 h/day, 5 days/wk, 30 m/min, 7% grade for 5 wk) on the expression of myosin heavy chain (MHC) isoforms during and after regeneration of a fast-twitch white muscle [extensor digitorum longus (EDL)]. Male Wistar rats were randomly assigned to a sedentary (n = 10) or an endurance-trained (ET; n = 10) group. EDL muscle degeneration and regeneration were induced by two subcutaneous injections of a snake toxin. Five days after induction of muscle injury, animals were trained over a 5-wk period. It was verified that ~40 days after venom treatment, central nuclei were present in the treated EDL muscles from sedentary and ET rats. The changes in the expression of MHCs in EDL muscles were detected by using a combination of biochemical and immunocytochemical approaches. Compared with contralateral nondegenerated muscles, relative concentrations of types I, IIa, and IIx MHC isoforms in ET rats were greater in regenerated EDL muscles (146%, P < 0.05; 76%, P < 0.01; 87%, P < 0.01, respectively). Their elevation corresponded to a decrease in the relative concentration of type IIb MHC (36%, P < 0.01). Although type I accounted for only 3.2% of total myosin in regenerated muscles from the ET group, the cytochemical analysis showed that the proportion of positive staining with the slow MHC antibody was markedly greater in regenerated muscles than in contralateral ones. Collectively, these results demonstrate that the regenerated EDL muscle is sensitive to endurance training and suggest that the training-induced shift in MHC isoforms observed in these muscles resulted from an additive effect of regeneration and repeated exercise.