Gravitational unloading is known to produce changes in the expression of a number of contractile and regulatory proteins in the soleus muscle. This applies particularly to isoforms of myosin heavy chains (MHC) and SERCA sarcoplasmic reticulum calcium pumps. Unloading increases the resting levels of extracellular calcium in soleus muscle fibers. The present study addresses verification of the hypothesis that changes in the expression of MHC and SERCA isoforms in gravitational unloading are linked with the accumulation of calcium ions in the myoplasm of muscle fibers. It is suggested that specific blockade of L-type calcium channels using nifedipine decreases the myoplasmic calcium ion concentration, thus preventing the development of changes in the expression of MHC and SERCA isoforms. A total of 36 male Wistar rats were divided into three groups: a control group, an unloading group using the Morley-Holton soleus muscle functional unloading model, and an unloading + nifedipine group, where animals received daily nifedipine (7 mg/kg/day) with their drinking water on the background of suspension. The results showed that blockade of L-type calcium channels on the background of gravitational unloading significantly decreased the extent of calcium ion accumulation in the myoplasm of soleus muscle fibers, which partly prevented the transformation of muscle fibers (in relation to the fast and slow isoforms of MHC and SERCA) to the rapid type. There was no nuclear translocation of the greater part of transcription factor NFATc1, as seen on unloading.
Exposure to actual or simulated microgravity considerably changes the structure and function of mammalian muscle fibers (MFs), the most pronounced changes being a decrease in the sizes of the fibers and its contractile apparatus (atrophy), as well as qualitative and quantitative changes in myosin and the sarcomeric cytoskeletal proteins titin and nebulin [1][2][3][4]. In the sarcomere, titin binds with myosin-containing filaments to form an elastic connection between them and the Z band, thereby partly determining the elastic properties of the muscle. Nebulin binds with actin-containing filaments. Along with studying changes in myosin, determining the role of these proteins under gravitational unload is an urgent task.The maintenance of the contractile activity of MFs is necessary to prevent their destructive changes under gravitational unload. The maintenance of the contractile activity of postural-tonic MFs under the conditions of normal earth's gravity is ensured by the impulse activity of small motoneurons of the anterior horns of the spinal cord, which, in turn, is controlled by both central signals and the afferent control system. The system of deep skin sense (support perception) and the proprioceptors of both tonic extensors themselves and their antagonists (flexors) are the main afferent systems controlling the activity of tonic motoneurons [2,5,6]. Under gravitational unload, the afferent input from the legs is decreased by 25% [7], with the background activity of the m. soleus being also decreased and that of the m. tibialis anterior being increased [7,8]. In our previous study [9], we compared the changes in the muscle phenotype under gravitational unload (suspension) and under the unload combined with the surgical deafferentation of the leg (by ablating sensory ganglia from the lumbar region of the spinal cord). In the case of gravitational unload alone, the myosin phenotype of the fibers was shifted towards the fast type (i.e., the percentage of fibers containing fast-type heavy chains of myosin was increased); if suspension was combined with deafferentation, the myosin phenotype was shifted back towards the slow type, with the percentage of fibers containing slow-type myosin chains exceeding even the control value. Obviously, the only difference between the mechanisms of these two effects is the increase in the activity of flexor muscles and, hence, the afferent input from these muscles caused by gravitational unload.On the basis of these results and literature data, we put forward the hypothesis that the influence of flexor centers activated by gravitational unload accounted for the suppression of the activity of the m. soleus and the subsequent changes in its structural and metabolic profile. We supposed that the imposed functional unload of flexors would eliminate the suppression of the motoneurons controlling the m. soleus and prevent atrophic processes. Here, we tested this hypothesis.The experiment was performed according to the current regulations of handling laboratory animals and was appro...
The aim of the present work was to assess the contributions of the reflex and local components to preventing decreases in the size and changes in the ratio of fibers containing the slow and fast isoforms of myosin heavy chains during chronic stretching of a postural muscle in rats in conditions of gravitational unloading. A unilateral surgical deafferentation method was used. The results demonstrated that deafferentation of the hindlimb had no effect on preventing reductions in muscle fiber size in conditions of chronic muscle stretching in conditions of gravitational unloading. The results obtained from these experiments did not support the hypothesis that the predominant contribution to preventing the development of atrophic changes comes from activation of muscle afferents in chronic stretching of the unloaded muscle. Deafferentation of both suspended animals and those with normal motor activity led to increases in the proportion of soleus muscle fibers containing the slow isoforms of myosin heavy chain.
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