Slow myosin heavy chain expression in the absence of muscle activity

1 EA300, Université Paris Diderot, Paris; 2 Institut National de la Santé et de la Recherche Médicale, U787, Paris; 3 Faculté de Médecine, Université Pierre et Marie Curie, Unité Mixte de Recherche S787, Paris; 4 Institut de Myologie, Paris; 5 Généthon, Évry; and 6 Université Paris Descartes, Paris, France Submitted 6 August 2008 ; accepted in final form 20 October 2008 Innervation has been generally accepted to be a major factor involved in both triggering and maintaining the expression of slow myosin heavy chain (MHC-1) in skeletal muscle. However, previous findings from our laboratory have suggested that, in the mouse, this is not always the case (30). Based on these results, we hypothesized that neurotomy would not markedly reduced the expression of MHC-1 protein in the mouse soleus muscles. In addition, other cellular, biochemical, and functional parameters were also studied in these denervated soleus muscles to complete our study. Our results show that denervation reduced neither the relative amount of MHC-1 protein, nor the percentage of muscle fibers expressing MHC-1 protein ( P > 0.05). The fact that MHC-1 protein did not respond to muscle inactivity was confirmed in three different mouse strains (129/SV, C57BL/6, and CD1). In contrast, all of the other histological, biochemical, and functional muscle parameters were markedly altered by denervation. Cross-sectional area (CSA) of muscle fibers, maximal tetanic isometric force, maximal velocity of shortening, maximal power, and citrate synthase activity were all reduced in denervated muscles compared with innervated muscles ( P < 0.05). Contraction and one-half relaxation times of the twitch were also increased by denervation ( P < 0.05). Addition of tenotomy to denervation had no further effect on the relative expression of MHC-1 protein ( P > 0.05), despite a greater reduction in CSA and citrate synthase activity ( P < 0.05). In conclusion, a deficit in neural input leads to marked atrophy and reduction in performance in mouse soleus muscles. However, the maintenance of the relative expression of slow MHC protein is independent of neuromuscular activity in mice. skeletal muscle; tenotomy; force; slow myosin heavy chain; power; velocity of shortening; oxidative capacity; atrophy Address for reprint requests and other correspondence: A. Ferry, UMR 787, Université Pierre et Marie Curie, 105 Ave. de l'Hôpital 75013 Paris, France (e-mail: Arnaud.Ferry{at}univ-paris5.fr )