[Role of calcium-dependent mechanisms in the development of atrophy in postural muscle deprived of gravitational loading].

Downsizing of muscle fibers, decline of their contractility and alteration of the myosin phenotype towards fast isoforms prevalence are ranked among the main consequences of gravitational unloading of postural muscles. Role of Ca2+ ions in these processes is the subject of the article. Authors revealed increase in the Ca2+ content in myofibers of resting m. soleus of mice following hindlimb suspension. It has been also reported earlier that nifedipine, a specific blocker of calcium L-channels, can prevent this increase acting on the central and local controls. Therefore, a supposition can be made that activation of the dehydropyridine Ca channels is responsible for Ca2+ rest accumulation during gravitational unloading. The calcium-dependent signaling pathways may be thought of as key players in a number of developments due to gravitational unloading. To begin with, already in early 1990s this role in the hypogravity-induced muscle atrophy was ascribed to calpains, Ca-dependent proteinases which was clearly demonstrated later. We observed maintenance of the relative titin and nebulin contents in unloaded m. soleus associated with the effect of Ca chelators. Also, nifedipine injection reduced significantly the growth of MHC fast isoforms expression during gravitational unloading equally on the RNA and protein levels. To bring to light the place of calcineurin/NFAT signaling system in the MHC phenotype alteration, we undertook inhibition of this pathway by injection of cyclosporine A. This resulted in getting evidence of the stabilizing function of this pathway as it opposes to the myosin phenotype transformation to the fast one.