Tomoo Yoshinaga

Gravitational unloading effects on muscle fiber size, phenotype and myonuclear number

The effects of gravitational unloading with or without intact neural activity and/or tension development on myosin heavy chain (MHC) composition, cross-sectional area (CSA), number of myonuclei, and myonuclear domain (cytoplasmic volume per myonucleus ratio) in single fibers of both slow and fast muscles of rat hindlimbs are reviewed briefly. The atrophic response to unloading is generally graded as follows: slow extensors > fast extensors > fast flexors. Reduction of CSA is usually greater in the most predominant fiber type of that muscle. The percentage of fibers expressing fast MHC isoforms increases in unloaded slow but not fast muscles. Myonuclear number per mm of fiber length and myonuclear domain is decreased in the fibers of the unloaded predominantly slow soleus muscle, but not in the predominantly fast plantaris. Decreases in myonuclear number and domain, however, are observed in plantaris fibers when tenotomy, denervation, or both are combined with hindlimb unloading. All of these results are consistent with the view that a major factor for fiber atrophy is an inhibition or reduction of loading of the hindlimbs. These data also indicate that predominantly slow muscles are more responsive to unloading than predominantly fast muscles.

The Role of Neural and Mechanical Influences in Maintaining Normal Fast and Slow Muscle Properties

The relative importance of neural and mechanical influences in maintaining normal slow and fast muscle properties remains unclear. To address this issue, we studied the effects of 10 days of hindlimb unloading (HU) with or without tenotomy and/or denervation on the cross-sectional area (CSA), myosin heavy chain (MHC) expression (immunohistochemistry) and composition (gel electrophoresis), and myonuclear number in soleus and plantaris fibers in adult male Wistar rats. In general, the adaptations in fiber type and size were similar using either single fiber gel or immunohistochemical analyses. HU resulted in atrophy of type I and I+IIa/x MHC fibers in the soleus and in type I, I+IIa/x, IIa/x, IIa/x+IIb, and IIb MHC fibers in the plantaris. Addition of tenotomy and/or denervation in HU rats had minimal effects on fiber CSA in the soleus, but fiber CSA in the plantaris further decreased, particularly in fibers expressing only fast MHCs. HU resulted in a de novo appearance of type I+IIa/x+IIb and IIa/x+IIb MHC fibers in the soleus and of type I+IIa/x+IIb MHC fibers in the plantaris.Tenotomy and/or denervation in HU rats had no further effect on the fiber type composition of either muscle. Mean myonuclear number/mm of type I fibers was decreased in the soleus of HU rats, and increased in type I and I+IIa/x fibers in HU plus tenotomy (HU+Ten) rats. In the plantaris, mean myonuclear number/mm of type IIa/x, IIa/x+IIb, and IIb fibers was lower after HU with or without tenotomy and/or denervation. Mean cytoplasmic volume/myonucleus ratio of type I and I+IIa/x fibers in the soleus of the HU group tended to be smaller than in controls. The largest decrease was noted in the HU+Ten group. In the plantaris, this ratio was unaffected by HU alone, but was decreased by addition of tenotomy and/or denervation when all fiber types were combined. These data indicate that the major cause of fiber atrophy and adaptations in myonuclear domain size in the slow soleus of HU rats is the chronic reduction in force generation, whereas the elimination of neuromuscular contact via denervation results in additional fiber atrophy and adaptations in myonuclear domain size in the fast plantaris.