TY - JOUR

T1 - Short-Term Hypobaric Hypoxia Isoform-Specifically Protects Rat Skeletal Muscle Na,K-ATPase From Disuse-Induced Dysfunction

AU - Кравцова, Виолетта Васильевна

AU - Ганке, Дарья Дмитриевна

AU - Тишкова, Мария Вячеславовна

AU - Сабурова, Екатерина Андреевна

AU - Матыцин, Вячеслав

AU - Кривой, Игорь Ильич

PY - 2024/10/30

Y1 - 2024/10/30

N2 - Hypoxic preconditioning is known to protect against various functional disorders, including skeletal muscle dysfunction. Na,K-ATPase, which plays an important role in adaptation to hypoxia, is critical for maintaining the performance of skeletal muscles, which co-express the α1 and α2 isozymes of the enzyme. Persistent dysfunction of α2 Na,K-ATPase isozyme is characteristic of the motor inactivity of skeletal muscles. In this study, we tested our hypothesis that mild hypoxia is able to improve Na,K-ATPase in disused soleus muscle. Rats were subjected to simulated high-altitude (3000 m above sea level) hypobaric hypoxia (HH) for 3 h using a hypobaric chamber. Then, 18 h after control or HH conditions, rats were subjected to 6 h of hindlimb suspension (HS), a model of skeletal muscle disuse. Isolated soleus muscles were tested. HH itself stably increased the α2 Na,K-ATPase isozyme membrane abundance and its electrogenic activity. These effects were accompanied by a decrease in serum level of circulating endogenous ouabain, a specific ligand for Na,K-ATPase. HS itself caused loss of electrogenic activity of α2 Na,K-ATPase, but pretreatment with HH protected against this impairment. This protective effect was accompanied by an increase in the α2 Na,K-ATPase membrane abundance without a change in total protein content, suggesting an increase in the α2 Na,K-ATPase traffic from the intracellular pool to the sarcolemma; serum ouabain level was significantly increased. We suggest that these findings open a new field for further studies and may have therapeutic implications for disuse-induced skeletal muscle pathology.

AB - Hypoxic preconditioning is known to protect against various functional disorders, including skeletal muscle dysfunction. Na,K-ATPase, which plays an important role in adaptation to hypoxia, is critical for maintaining the performance of skeletal muscles, which co-express the α1 and α2 isozymes of the enzyme. Persistent dysfunction of α2 Na,K-ATPase isozyme is characteristic of the motor inactivity of skeletal muscles. In this study, we tested our hypothesis that mild hypoxia is able to improve Na,K-ATPase in disused soleus muscle. Rats were subjected to simulated high-altitude (3000 m above sea level) hypobaric hypoxia (HH) for 3 h using a hypobaric chamber. Then, 18 h after control or HH conditions, rats were subjected to 6 h of hindlimb suspension (HS), a model of skeletal muscle disuse. Isolated soleus muscles were tested. HH itself stably increased the α2 Na,K-ATPase isozyme membrane abundance and its electrogenic activity. These effects were accompanied by a decrease in serum level of circulating endogenous ouabain, a specific ligand for Na,K-ATPase. HS itself caused loss of electrogenic activity of α2 Na,K-ATPase, but pretreatment with HH protected against this impairment. This protective effect was accompanied by an increase in the α2 Na,K-ATPase membrane abundance without a change in total protein content, suggesting an increase in the α2 Na,K-ATPase traffic from the intracellular pool to the sarcolemma; serum ouabain level was significantly increased. We suggest that these findings open a new field for further studies and may have therapeutic implications for disuse-induced skeletal muscle pathology.

UR - https://link.springer.com/article/10.1134/S0022093024050053

U2 - 10.1134/s0022093024050053

DO - 10.1134/s0022093024050053

M3 - Article

VL - 60

SP - 1712

EP - 1724

JO - Journal of Evolutionary Biochemistry and Physiology

JF - Journal of Evolutionary Biochemistry and Physiology

SN - 0022-0930

ER -