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1 UFR Staps, University Paris 5, Paris, France; EA 2363, University Paris 13, Bobigny, France
2 FRE 2853, CNRS, Paris, France; UFR Staps, University Paris 5, Paris, France
3 FRE 2853, CNRS, Paris, France
4 EA 300, University Paris 7, Paris, France
* To whom correspondence should be addressed. E-mail: agbulut{at}larib.inserm.fr.
In the literature there is an ambiguity as to the respective roles played by calcineurin phosphatase activity (CPA) and muscle innervation in the re-establishment of the slow muscle phenotype following muscle regeneration in different species. In this study, we wanted to determine the role of calcineurin and muscle innervation on the appearance and maintenance of the slow phenotype during mouse muscle regeneration. The pattern of myosin expression and CPA were analyzed in adult (n=15), regenerating (n=45) and denervated-regenerating (n=32) slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles. Moreover, in a second group of denervated-regenerating mice (n=9), the animals were treated with a calcineurin inhibitor. Regeneration was induced by injection of cardiotoxin and in the denervated-regenerating group, denervation was carried out by cutting the sciatic nerve prior to the administration of cardiotoxin. In innervated-regenerating soleus muscle, CPA increased continuously after 10 days post-injury and by 21 days there was a 3.5 folds increase in CPA compared to adult basal level whereas in innervated-regenerating EDL muscle CPA remained unchanged. Moreover, our results show that in denervated-regenerating muscles the MyHC profile was identical in spite of the functional differences inherent these muscles. In long-term denervatedregenerating muscles a slow muscle phenotype was re-expressed both in the presence or absence of calcineurin inhibitor. Our results show that although in innervated-regenerating mouse muscle the appearance of a slow phenotype is correlated with a peak of CPA, in denervated-regenerating muscles a slow phenotype is triggered and maintained in a calcineurin and nerve independent manner.
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