Department of General Physiology, Saint Petersburg State University, 199034 Saint Petersburg, Russia.
Department of Pharmacology and Pharmacy, Mechnikov North-Western State Medical University, 191015 Saint Petersburg, Russia.
Int J Mol Sci. 2022 Oct 6;23(19):11869. doi: 10.3390/ijms231911869.
The Na,K-ATPase plays an important role in adaptation to hypoxia. Prolonged hypoxia results in loss of skeletal muscle mass, structure, and performance. However, hypoxic preconditioning is known to protect against a variety of functional impairments. In this study, we tested the possibility of mild hypoxia to modulate the Na,K-ATPase and to improve skeletal muscle electrogenesis. The rats were subjected to simulated high-altitude (3000 m above sea level) hypobaric hypoxia (HH) for 3 h using a hypobaric chamber. Isolated diaphragm and soleus muscles were tested. In the diaphragm muscle, HH increased the α2 Na,K-ATPase isozyme electrogenic activity and stably hyperpolarized the extrajunctional membrane for 24 h. These changes were accompanied by a steady increase in the production of thiobarbituric acid reactive substances as well as a decrease in the serum level of endogenous ouabain, a specific ligand of the Na,K-ATPase. HH also increased the α2 Na,K-ATPase membrane abundance without changing its total protein content; the plasma membrane lipid-ordered phase did not change. In the soleus muscle, HH protected against disuse (hindlimb suspension) induced sarcolemmal depolarization. Considering that the Na,K-ATPase is critical for maintaining skeletal muscle electrogenesis and performance, these findings may have implications for countermeasures in disuse-induced pathology and hypoxic therapy.
钠钾-ATP 酶在适应低氧环境中起着重要作用。长时间的低氧会导致骨骼肌质量、结构和功能的丧失。然而，低氧预适应被认为可以预防多种功能障碍。在这项研究中，我们测试了轻度低氧调节钠钾-ATP 酶并改善骨骼肌发电的可能性。使用减压室使大鼠处于模拟高海拔（海拔 3000 米以上）低氧（HH）环境中 3 小时。检测了分离的膈肌和比目鱼肌。在膈肌中，HH 增加了α2 钠钾-ATP 酶同工型的电活性，并稳定地超极化了 24 小时的连接外膜。这些变化伴随着硫代巴比妥酸反应物质的产生稳定增加，以及血清内源性哇巴因水平（钠钾-ATP 酶的特异性配体）下降。HH 还增加了α2 钠钾-ATP 酶的膜丰度，而不改变其总蛋白含量；质膜脂质有序相没有改变。在比目鱼肌中，HH 防止了废用（后肢悬吊）引起的肌膜去极化。考虑到钠钾-ATP 酶对维持骨骼肌发电和功能至关重要，这些发现可能对废用性病理和低氧治疗的对策有意义。
