In the 1930—1940s R. G. Leibson and A. G. Ginеtsinsky with colleagues carried out the experiments were it was shown that the changes in tenotomized rabbit soleus muscle are completely eliminated if the nerve is cut at the same time. The authors concluded that atrophy from inactivity is not a passive process, but it is an active result of neural influences which are carried out by the ventral roots of sciatic nerve. The nature of these influences has not been studied and nervous control is not clear. The present study was carried out on 2-month old Californian rabbits to confirm the described phenomenon and to investigate the assumed neurotrophic mechanisms. The morphological signs of atrophy and degeneration of tenotomized rabbit muscles, muscle fiber death of and growth of connective tissue were eliminated on day 11 of exposure by simultaneous Achilles tenotomy. The effect of colchicine application on the tenotomized muscle was almost the same as denervation (10 mM solution was applicated at the sciatic nerve for 10 min), but in the case of colchicine the degenerative changes were more pronounced. Denervation of the tenotomized muscle or colchicine application maintained the fast fiber cross-sectional area at the level of intact control. Sciatic nerve denervation or colchicine application prevented the rise in soleus muscle TrkB and TrkС expression and altered some neurotrophin expression. Denervation with tenotomy decreased TrkB mRNA expression by 3.4 times (p < 0.05), TrkC — by 3.2 times (p < 0.05), NT3-by 3.4 times (p < 0.05) compared with the tentotomized contralateral limb, colchicine with tenotomy — by 3.6 and 2.9 times respectively (p < 0.05).

A gender analysis has been carried out to analyze changes in intracellular signaling pathways that lead to the development of chronic alcoholic myopathy. It is known that acute or chronic alcohol intoxication can result in alcohol-induced lesions in skeletal muscles. Chronic alcoholic myopathy occurs much more frequently and can develop either independently or in combination with other forms of alcoholic disease (liver and heart lesions, malabsorption syndrome, or alcohol polyneuropathy). This disease is manifested by atrophy of skeletal muscles and a performance decrement. Most of the studies on the pathogenesis of chronic alcoholic myopathy have been carried out on male patients. Studies on alcoholic myopathy-induced muscle damage in females have not been previously reported.

Chronic alcoholic myopathy (CAM) is a common manifestation of alcoholic disease; however, the pathogenesis of the former has not been fully investigated. The main mechanism for the development of CAM is postulated to be impaired protein synthesis in the muscle fibers. A comprehensive clinical, biochemical, electromyographic, and morphological examination was made in 51 patients with chronic alcoholic intoxication. Morphological and morphometric studies were shown to play a determining role in the diagnosis of CAM. The clinical manifestations of skeletal muscle involvement corresponded to the magnitude of the atrophic process. Abnormalities were found in the basic components of protein synthesis at both the intracellular and systemic levels of regulation.

The article tells about the results of a comprehensive study of 24 patients with chronic alcoholic intoxication; pathogenesis and clinical pattern of alcoholic polyneuropathy and myopathy; the leading role of morphological and morphometric study in the diagnosis of chronic alcoholic myopathy; evaluation of efficacy of alcohol polyneuropathy treatment with neurotropic vitamin group B medicines.

The simulation model of “dry” immersion was used to evaluate the effects of plantar mechanical stimulation (PMS) and high frequency electromyostimulation (EMS) on the mechanical properties of human soleus fibers under the conditions of gravitational unloading. We examined contractile properties of single fibers by means of tensometry, transversal stiffness of sarcolemma and different areas of the contractile apparatus by means of atomic force microscopy. It was shown that there is a reduction of transversal stiffness in single muscle fibers under hypogravitational conditions. Application of different countermeasures could compensate this effect. Meanwhile pneumostimulation and electro stimulation act in quite different way. Therefore, pneumostimulation seems to be more effective. The data obtained can be considered as the evidence of the fact that such countermeasures as PMS and electromyostimulation influence on muscle fibers in quite different ways and PMS efficiency is likely to be higher. On the basis of our experimental data on transverse stiffness of mechanotransductional nodes and the contractile apparatus, we can assume that support stimulation allows prevention of destructive processes in muscle fibers. Electrostimulation seems to stimulate contractile activity only without suppression of impairment of the fiber mechanical properties.

It has been shown that the modulation of the mechanical properties of sarcolemma mediated by nifedipine may be related to the dynamics of accumulation of calcium ions under short-term rat hindlimb suspension. The basal calcium level was measured with a fluorescent probe Fluo-4AM, the transverse stiffness of different parts of the contractile apparatus and sarcolemma was estimated by atomic force microscopy, and the content of desmin was determined by gel electrophoresis with immunoblotting. It has been found that nifedipine has a protective effect on muscle fibers under hypogravity by decreasing the degradation of desmin and proteins that determine the transverse stiffness of sarcolemma and the contractile apparatus, and the intensity of the increase in the basal calcium level. It was shown that selective blocking of L-channels leads to an increase in the basal calcium level in intact soleus fibers. At the same time, the transverse stiffness of sarcolemma and the contractile apparatus increases. The mechanism of this increase is still unclear, but it is thought to mediate the protective action of nifedipine.

The concentration of calcium ions in soleus muscle fibers in Mongolian gerbils and rats has been shown to increase for the first day of gravitational load by 4.5 and 2.8 times, respectively, compared to the control. This increase is preserved for 3 days, while, after 12 days, it decreases, but remains above the control level. The resting calcium level in the control in gerbils is lower than in rats and, as a consequence, its change for the first day of unloading is greater. It is possible that this leads to earlier changes in the muscle fiber isoform composition in gerbils; a statistically significant shift in the ratio of fibers that contain fast and slow calcium pumps towards pumping faster is noted as early as the first day, while that of fibers that express the corresponding isoforms of myosin heavy chains (MHCs) is observed after 3 days of functional unloading. In rats, similar changes are revealed as late as on the 7th day. After 12 days, in both species, a tendency to return to the control level is observed that is more pronounced in gerbil.

A comparative investigation of the dynamics of contractile properties of the whole soleus muscle and its fibers during 3- and 12-day-long hind limb suspension of Wistar rats and Mongolian gerbils (Meriones unguiculatus) has been performed. The data obtained indicate that the structural and functional changes caused by hypogravity in gerbils are slowed down compared with rats. A very intensive drop in water containment in gerbils was found, which can cause shifts in the ionic strength of the intracellular space of the muscle fiber. As a result, the photolytic activity of different enzymes may change, which can induce a less pronounced reduction in Z-disc and M-line stiffness and contractile capabilities in gerbils compared to rats.

In this study, it was shown that calcium levels in the fibers of m. soleus of Mongolian gerbils after one day of unloading increased four and a half times in comparison with the control. In rats, the situation differed: 2.8 times increase after the 1st day of hypogravity persisted until the 3rd day and then calcium levels slightly decreased to the 12th day. However, the base concentrations of calcium in the control group of gerbils were significantly lower than in control rats, thus there was larger shift of this parameter during the first day. Probably, this was the reason for an earlier start of the protein phenotype shift in gerbils: statistically significant increase in the number of fibers with "fast" SERCA isoforms was detected after one day of unloading and therefore slow-to-fast shift in myosin phenotype was observed on the 3rd day of unloading. The same changes in rat muscle could be detected only after the 7th and the 12th day, respectively. In both species, there was a tendency to restore their initial parameters to the 12th day but in gerbils it was much more intensive.

Some of the electrophysiological parameters of m. soleus of rat and Mongolian gerbil, and Ca ions content in fiber myoplasm were compared in different periods of gravitational unloading simulated by tail-suspension. No difference was found between the control animals as for membrane potential at rest, electrogenic activities of Na-K-ATPase and its isoforms, and input resistance of m. soleus fibers. At the same time, unlike rats, gerbils exhibited a substantial Ca decrease in myoplasm. From day one to 14 of gravitational unloading the pace of electrophysiological changes in gerbil's m. soleus was noticeably slower than of rat's, whereas Ca ions depositing in myoplasm was observed in both species already at the beginning ofsuspension. Analysis of the results suggests that adaptive changes in m. soleus of Mongolian gerbil and rat during simulated gravitational unloading are fundamentally different due to, probably, peculiar water-electrolyte metabolism, type of locomotion, and other factors which are still unclear.

Gravitational unloading leads to destructive changes in the structure and function of muscle fibers. However, the role of the EMG activity level is still unclear. We measured changes caused by one- and three-day hypogravity in the following muscles: Soleus (Sol), Tibialis anterior (TA) and Gastrocnemius c.m. (MG). We used Wistar rats and Mongolian gerbils. The following parameters were assessed: the specific force of contraction of isolated fibers by tensometry, the transverse stiffness of the contractile apparatus by atomic force microscopy, and the calcium content by Fluo-4. We detected the accumulation of calcium ions in all muscles even after one-day unloading. In Sol this effect was more significant than in other muscles. After one-day of hypogravity we detected an increase in the specific force in all muscle types and species. Meanwhile, the transverse stiffness of the contractile apparatus, M-band and Z-disc increased only in fast muscles but not in Sol. After three-days of unloading, the specific force in Sol decreased, and the transverse stiffness of the contractile apparatus behaved in the same way as the force. The specific tension of fast muscle fibers decreased significantly in comparison with one-day unloading. In addition, the transverse stiffness of some areas of MG had a tendency to decrease in comparison to “one-day” unloading, although there was no such a tendency in the fibers of TA. In Mongolian gerbils the tendencies were the same as in the rats, but showed less dramatic changes. The reduction in the magnitude of changes in the Sol–MG–TA series correlates with EMG activity.

After three days of hind limb unloading, the depolarization of muscle fibers from -71.0 +/- 0.5 mV to -66.8 +/- 0.7 mV as well as a decrease in muscle excitability and a trend to fatigue acceleration were observed. After hind limb unloading, the electrogenic contribution of the ouabain-sensitive alpha2 isoform of Na,K-ATPase, tested as depolarization due to the administration of 1 microM ouabain, decreased from 6.2 +/- 0.6 to 0.5 +/- 0.8 mV. The contribution of the ouabain-resistant alpha1 isoform, estimated as additional depolarization after the administration of 500 microM ouabain, decreased from 4.6 +/- 0.6 to 2.6 +/- 0.6 mV. After hind limb unloading, the fluorescence intensity of single muscle fibers loaded with Fluo-4-AM increased more than four times, indicating an increase in intracellular Ca2+ concentration. The effect was prevented by local delivery of nifedipine, which blocks L-type Ca2+ channels. These data suggest the existence of a selective mechanism of suppression of the alpha2-pump electrogenic contribution, which led to the depolarization of soleus muscle fibers after 3 days of hind limb unloading. The depolarization in turn may activate L-type Ca2+ channels, resulting in intracellular Ca2+ accumulation.

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.