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

Hypoxic preconditioning is known to protect against variousfunctional disorders, including skeletal muscle dysfunction. Na,K-ATPase,which plays an important role in adaptation to hypoxia, is critical formaintaining the performance of skeletal muscles, which co-expressthe α1 and α2 isozymes of the enzyme. Persistent dysfunction ofα2 Na,K-ATPase isozyme is characteristic of the motor inactivityof skeletal muscles. In this study, we tested our hypothesis thatmild hypoxia is able to improve Na,K-ATPase in disused soleus muscle.Rats were subjected to simulated high-altitude (3000 m above sealevel) hypobaric hypoxia (HH) for 3 h using a hypobaric chamber.Then, 18 h after control or HH conditions, rats were subjected to6 h of hindlimb suspension (HS), a model of skeletal muscle disuse.Isolated soleus muscles were tested. HH itself stably increasedthe α2 Na,K-ATPase isozyme membrane abundance and its electrogenicactivity. These effects were accompanied by a decrease in serumlevel 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. Thisprotective effect was accompanied by an increase in the α2 Na,K-ATPasemembrane abundance without a change in total protein content, suggestingan increase in the α2 Na,K-ATPase traffic from the intracellularpool to the sarcolemma; serum ouabain level was significantly increased.We suggest that these findings open a new field for further studiesand may have therapeutic implications for disuse-induced skeletalmuscle pathology.