Целью обзора является описание механизмов работы АТФ-зависимых путей регуляции сигналлинга скелетных мышц при их функциональной разгрузке. Особое внимание уделяется описанию роли паннексиновых каналов, P2Y-пуринэргических рецепторов и IP3-рецепторов в активации специфических транскрипционных сигнальных программ m. soleus при ее функциональной разгрузке. Известно, что при функциональной разгрузке мышц происходит накопление макроэргических фосфатов (АТФ, креатинфосфата) и ионов Ca в мышечных волокнах. Ранее показано, что введение при моделировании функциональной разгрузки препарата, снижающего в мышце уровень макроэргических фосфатов, а также уровень кальция, предотвращает трансформацию мышечных волокон в «быструю» сторону и снижает степень ее атрофии. Предлагаемый обзор описывает возможные механизмы, с помощью которых АТФ достигает рецепторов, воспринимающих этот сигнал, а также способ его передачи для запуска «медленного» Ca2+-сигнала, участвующего в активации специфических транскрипционных программ в мышце при моделировании ее функциональной разгрузки.

Various forms of muscle unloading can be found in patients with prolonged bed rest, with strokes and spinal lesions, during muscle immobilization in traumatology, in zero gravity, etc. During unloading, basically, postural muscles (for example, soleus) are affected. The rearrangement of skeletal muscles during unloading is based on their atrophy due to an increase in proteolysis and a decrease in the intensity of protein synthesis [1, 2]. The review is devoted to the study of the histone deacetylases I and IIa (HDAC1, HDAC 4/5) role, as well as the MAPK38 signaling pathway in the activation of transcription factors FOXO and myogenin, which are involved in the expression of E3 ubiquitin ligases genes atrogin-1 and MuRF-1 under skeletal muscle unloading.

Some steps of anabolic and catabolic signaling pathways were investigated in postural/tonic m. longissimus dorsi of mice following the 30-day orbital flight of biosatellite "Bion-M1" and 8-day recovery. Western blotting was used for determining insulin receptor substrate 1 (IRS-1) and AMR-activated protein kinase (AMPK) involved in reciprocal regulation of anabolic and catabolic pathways, as well as E3-ligase MURF-1, and elongation factor eEF2. Functioning of the IGF-1-dependent IRS-1 signaling pathway was activated in the recovery period only. Though the content of ubiquitinligase MURF-1 showed an increase after flight, on completion of the recovery period it did not exceed the pre-flight level unambiguously.

The review is dedicated to the signaling pathways triggered by the nitric oxide II in skeletal muscle. Analysis of the current literature shows that during physical exercise of various intensity and regimen the nitric oxide is an essential trigger of the signaling pathways, leading to the alteration of the structural and metabolic myofiber profile and enhancement of its functional capacity. At the same time during the elevated muscle contractile activity (for instance, eccentric activity), NO serves as a protective and stabilizing agent, preventing from the intensification of the proteolytic processes. Data obtained from the experiments with the modulation of the NO at the background of the functional (gravitational) unloading give evidence that neuronal NO synthase activation in this experimental conditions allows to stabilize the degradation pathways and prevent from disuse atrophy development.