The regeneration of adult rat and mouse slow (soleus) and fast (sternomastoid) muscles was examined after the degeneration of myofibers had been achieved by a snake venom cardiotoxin, under experimental conditions devised to spare as far as possible the satellite cells, the nerves, and the blood vessels of the muscles.Three days after the injury, no myosin was detectable in selected portions of the muscles. New myosins of embryonic, neonatal, and adult types started to be synthesized during the following two days. Adult myosins thus appeared more precociously than in development, which implies that the synthesis of myosin isoforms during regeneration does not entirely 'recapitulate' the sequence of myosin transitions observed during normal development.Two weeks after the injury, the isomyosin electrophoretic pattern displayed by regenerated muscles was already the same as that of control muscles; the normal adult pattern was therefore expressed more rapidly in regenerating than in developing muscles.Except for the synthesis of the slow isoform which was generally inhibited in denervated muscles, the same types of myosins were expressed during the early stages of regeneration in denervated as in innervated muscles; long-term denervation prevented however the qualitative and quantitative recovery of the normal myosin pattern.Regeneration of adult muscles is often considered as a recapitulation of the events which normally occur during myogenesis (for review see Plaghki [I]). A few studies have thus suggested that embryonic, neonatal, and adult myosins are successively synthesized during regeneration [2 -41 and display transitions analogous to those occurring during muscle development [5 -121. More recent results obtained after cold injury of chicken muscles [13, 141 indicate however some differences between the isoform transitions occurring in regenerating and in developing muscles.To explore this further, we have characterized the myosin forms which are synthesized in mammalian slow and fast muscles regenerating after injury by a cardiotoxin purified from the venom of Naja mossambica mossambica [15]. As the toxin was shown to spare the innervation of the muscle, we also examined the influence of the motor nerve on the regeneration, by comparing normally innervated muscles and muscles which had been denervated prior to toxin injury.Preliminary results of this work have been reported [16]. MATERIALS AND METHODS Muscle injuryExperiments were performed on adult Wistar rats and Swiss CF mice of about 200 g and 30 g respectively. Animals were anesthetized with chloral hydrate. Muscles (soleus and sternomastoid) were exposed by an incision of the overlying skin and injected with pure cardiotoxin (10 pM in 0.9% NaCl); the muscles were then bathed in the toxin for 5 min, after which they were perfused and washed with Ringer solution [15]. The muscles were removed, for isomyosin analysis, at various intervals, between 24 h and two months after the injury. As cardiotoxin was observed to spare a few myofibers in the deepest ...
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