Slow myosin heavy chain expression in the absence of muscle activity

Abstract

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 Ͼ 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 Ͻ 0.05). Contraction and one-half relaxation times of the twitch were also increased by denervation (P Ͻ 0.05). Addition of tenotomy to denervation had no further effect on the relative expression of MHC-1 protein (P Ͼ 0.05), despite a greater reduction in CSA and citrate synthase activity (P Ͻ 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 NEUROMUSCULAR ACTIVITY, INCLUDING both the neural and mechanical aspects, plays an important role in skeletal muscle physiology. It is now well established that increased chronic neuromuscular activity (physical training and electrical stimulation) induces beneficial adaptations in both muscle structure and function (for review, Refs. 23, 46). Moreover, there is a very large body of information showing that reduced neuromuscular activity (i.e., denervation, spinal cord isolation, disuse) causes important impairments in muscle function (for review, Refs. 20,41). For example, a reduction or the elimination of neural input results in muscle atrophy. Denervated slow muscles produce less maximal force and power, and the kinetics of the twitch is slower. This is accompanied by a reduction in oxidative capacity and a decrease in the relative expression of slow myosin heavy chain (MHC-1) protein (for review, Refs. 41, 53). However, it should be noted that most of this experimental data is derived from experiments on rats.MHC-1 protein is one of the major contractile proteins and is important for muscle function. A high level of MHC-1 expression in skeletal m...

Effect of locomotor training on muscle performance in the context of nerve–muscle communication dysfunction

“…The isometric contractile properties of soleus muscles were studied in vitro as previously described. 14,15 Mice were euthanized after removal of soleus muscles. Muscles were soaked in an oxygenated Krebs solution (95% O 2 and 5% CO 2 ) containing 58.5 mM NaCl, 24 mM NaHCO 3 , 5.4 mM KCl, 1.2 mM KH 2 PO 4 , 1.8 mM CaCl 2 , 1 mM MgSO 4 , and 10 mM glucose (pH 7.4), and maintained at a temperature of 22 C. One of the muscle tendons was attached to a force transducer (Harvard).…”

“…Other sections were used for immunohistochemistry, as previously described. 15,20 For determination of muscle fiber type, frozen unfixed sections were blocked for 1 h in a blocking solution (bovine serum albumin 4%, IgG free) and incubated overnight with a mouse monoclonal antibody directed against myosin heavy chain type 1 (MHC-1; 1/50; Hybridoma Bank). After washes in phosphate-buffered saline (PBS), sections were incubated for 1 h with secondary Alexa Fluor-conjugated anti-mouse IgG (1/400; Molecular Probes).…”

“…13 This severe neuromuscular fatigability 11,13,14 would markedly reduce the normal level of muscle activity of a postural and motor muscle such as the soleus muscle. Therefore, it is not surprising that absence of AChE causes muscle atrophy and reduction in maximal force, 14 as it does in denervation 15 and physical inactivity. 16 To reduce the muscle weakness induced by AChE deficiency, it is of interest to determine whether increased neuromuscular activity would have a beneficial effect on muscle performance.…”

“…We studied recovery of the soleus muscle after sciatic nerve injury because it is an antigravity muscle that is heavily recruited during locomotion. Our first hypothesis was that LT would improve muscle performance after nerve injuries that allow muscle reinnervation (nerve transection alone or crush), because muscle inactivity reduces contractility 15,16 and increased neuromuscular activity improves or accelerates nerve regeneration and muscle reinnervation. [4][5][6][7][8][9][10] Second, we examined whether LT would improve the performance of the permanently denervated soleus muscle (nerve transection with excision), as it was recently demonstrated that mechanical signals coming from passive stretch could reduce atrophy of denervated muscle 17 and thus, possibly, the deficit in maximal force production.…”

“…Our third hypothesis was that LT would improve soleus muscle performance of AChE-deficient mice exhibiting severe neuromuscular fatigability, 11,13,14 because reduced muscle activity leads to muscle weakness. 15,16 All these experiments were aimed to provide information on the potential beneficial effect of exercise on muscle weakness observed in the case of neuromuscular diseases affecting nerve-muscle communication.…”