From Activity to Inactivity and Back to Activity. Signaling Processes in the Postural Muscle in the Transition Period

Experiments with tail-suspended rats exposed to parabolic flight and human subjects in dry immersion repeatedly showed decreases, sometimes to the point of full inhibition, of the m. soleus electrical activity. The cessation of the activity, closely resembling the temporal physiological rest, which in rat m. soleus is normally 8–10 hours a day, is much longer in experiments and can be characterized as a state of inactivity. Already after 24 hours of inactivity, expression of the key muscle ubiquitin Е3 ligases increases with the simultaneous reductions in protein synthesis and translational capacity. Expression of the slow isoform of myosin heavy chains also decreases. The aim of the review is to summarize the data on the dynamics of molecular events in postural m. soleus of a mammal after cessation of its contractile activity. The changes in the complex of signaling pathways in the transitional period are triggered by a group of molecular messengers, which are directly dependent on the contractile activity. The function of increasing ATP concentration and ensuing reduction in phosphorylation of АМP-activated protein kinase (АМPК), as well as the expression of slow myosin, the regulators of mitochondrial and ribosome biogenesis and the resting membrane potential at the initial stage of muscle inactivity has been established. ATP-dependent processes contribute to NO reduction and Ca²⁺ ions accumulation in muscle fibers. The changes in these messengers precisely underlie the subsequent atrophic developments, transformation of myosin phenotype, muscle fiber atony and mitochondrial dysfunction. At the same time, after 3 days of inactivity, the postural muscle shows spontaneous activity with gradually increasing amplitude of electromyographic signals. The results of investigations of signaling processes in the postural muscle during the transition from activity to inactivity and back to autonomic activity suggest the difference and nonuniformity and nonlinearity of these processes and the change of mechanisms driving the destructive events.