title: Calcium-dependent signaling mechanisms and soleus fiber remodeling under gravitational unloading.
abstract: The decrease in postural muscle fiber size, diminishing of their contractile properties, slow-to-fast shift in myosin heavy chain expression pattern are known to be the main consequences of gravitational unloading. The Ca(2+) role in these processes has been studied for about 20 years. Ingalls et al. [J Appl Physiol 87(1):382-390, 1999] found the resting Ca(2+) level increase in soleus fibers of hindlimb unloaded mice. Results obtained in our laboratory showed that systemic or local application of nifedipine (L-type Ca(2+) channels' blocker) prevents Ca(2+) accumulation in fibers. Thus, activation of dihydropyridine calcium channels can be supposed to promote resting Ca(2+) loading under disuse. So, calcium-dependent signaling pathways may play an important role in the development of some key events observed under unloading. Since 90th the increased activities of Ca(2+)-dependent proteases (calpains) were considered as the crucial effect of hypogravity-induced muscle atrophy, which was proved later. We observed maintenance of titin and nebulin relative content in soleus muscle under unloading combined with Ca(2+) chelators administration. Nifedipine administration was shown to considerably restrict the slow-to-fast transition of myosin heavy chains (MHC) under unloading (at the RNA level and at the protein level as well). To clarify the role of calcineurin/NFAT signaling system in MHC pattern transition under unloading, we blocked this pathway by cyclosporine A application. Hereby, we demonstrated that calcineurin/NFAT pathway possesses a stabilizing function counteracting the myosin phenotype transformation under gravitational unloading.
authors.affiliation: SSC RF Institute for Biomedical Problems, RAS, Moscow, Russia. bshenkman@mail.ru
authors.forename: Boris S
authors.initials: BS
authors.lastname: Shenkman
authors.forename: T L
authors.initials: TL
authors.lastname: Nemirovskaya
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D006112:Gravitation; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D014893:Weightlessness
chemical_list: D002118:Calcium