Russian Journal of PhysiologyRussian Journal of PhysiologyРоссийский физиологический журнал им. И.М. Сеченова0869-81392658-655XThe Russian Academy of Sciences65154510.31857/S0869813923070117XILLSYEXPERIMENTAL ARTICLESЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИInfluence of the SERCA Activity on Rat’s Soleus Contractile Properties during Functional UnloadingВклад активности SERCA в изменение сократительных характеристик m. soleus крыс при функциональной разгрузкеSharloK. A.ШарлоК. А.Nemirovskaya@bk.ruLvovaI. D.ЛьвоваИ. Д.Nemirovskaya@bk.ruTyganovS. A.ТыгановС. А.Nemirovskaya@bk.ruZaripovaK. A.ЗариповаК. А.Nemirovskaya@bk.ruBelovaS. P.БеловаС. П.Nemirovskaya@bk.ruNemirovskayaT. L.НемировскаяТ. Л.Nemirovskaya@bk.ruInstitute of Biomedical Problems, RASИнститут медико-биологических проблем01072023109787288901022025Copyright ©; 2023, К.А. Шарло, И.Д. Львова, С.А. Тыганов, К.А. Зарипова, С.П. Белова, Т.Л. НемировскаяCopyright ©; 2023, К.А. Шарло, И.Д. Львова, С.А. Тыганов, К.А. Зарипова, С.П. Белова, Т.Л. Немировская2023К.А. Шарло, И.Д. Львова, С.А. Тыганов, К.А. Зарипова, С.П. Белова, Т.Л. НемировскаяК.А. Шарло, И.Д. Львова, С.А. Тыганов, К.А. Зарипова, С.П. Белова, Т.Л. Немировскаяhttps://journals.eco-vector.com/0869-8139/article/view/651545

Dysfunction of skeletal muscles and their atrophy during unloading are accompanied by excess calcium accumulation in the myoplasm of muscle fibers. We hypothesized that calcium accumulation may occur, among other reasons, due to inhibition of SERCA activity under muscle unloading. In this case, the use of a SERCA activator will reduce the calcium level in the myoplasm and prevent the consequences of unloading. Male Wistar rats were divided into 3 groups: vivarium control with placebo administration (C, n = 8), 7-day suspension group with placebo administration (7HS, n = 8) and 7-day suspension group with intraperitoneal administration of SERCA CDN1163 activator (50 mg/kg (7HS + CDN), n = 8). One m. soleus of each rat was frozen in liquid nitrogen, the second was tested for functional properties. In the 7HS group, increased soleus fatigue was found in the ex vivo test, a significant increase in mRNA and the number of fast muscle fibers, an increase in the level of calcium-dependent CaMK II phosphorylation and the level of tropomyosin oxidation, as well as a decrease in the content of mitochondrial DNA and protein. All these changes were prevented in the SERCA CDN1163 activator group. Conclusion: 7-day SERCA activator administration does not delay of soleus atrophy, but prevents the development of its fatigue, probably by preventing a decrease in the number of type I fibers and markers of mitochondrial biogenesis.

Нарушение функций скелетных мышц и их атрофия при функциональной разгрузке сопровождаются накоплением избыточного кальция в миоплазме мышечных волокон. Мы предположили, что накопление кальция может происходить, кроме прочих механизмов, из-за ингибирования работы Ca2+-АТФазы сарко/эндоплазматического ретикулума (SERCA) при разгрузке мышц. В этом случае применение активатора SERCA будет снижать уровень кальция в миоплазме и предотвращать последствия функциональной разгрузки. Самцы крыс были распределены на 3 группы – виварный контроль с введением плацебо (С, n = 8), группа 7-суточного вывешивания с введением плацебо (7НS, n = 8) и группа 7-суточного вывешивания с введением внутрибрюшинно активатора SERCA CDN1163 (50 мг/кг (7HS+CDN), n = 8). Одну m. soleus каждой крысы замораживали в жидком азоте, вторую тестировали на функциональные свойства. В группе 7HS обнаружили повышенную утомляемость soleus в тесте ex vivo, существенное увеличение мРНК и количества быстрых мышечных волокон, рост уровня кальций-зависимого фосфорилирования CaMK II и уровня окисления тропомиозина, а также снижение содержания митохондриальной ДНК и белка. Все эти изменения были предотвращены в группе с введением активатора SERCA CDN1163. Вывод: 7-суточное введение активатора SERCA предотвращает снижение индекса утомления m. soleus, вероятно, за счет предотвращения снижения количества волокон I типа и маркеров митохондриального биогенеза. Введение активатора SERCA не замедляет развития атрофии m. soleus.

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