AMP-activated protein kinase (AMPK) is a cellular energy gauge and a major regulator of cellular energy homeostasis. Once activated, AMPK stimulates nutrient uptake and the ATP-producing catabolic pathways, while it suppresses the ATP-consuming anabolic pathways, thus helping to maintain the cellular energy balance under energy-deprived conditions. As much as ~ 20–25% of the whole-body ATP consumption occurs due to a reaction catalysed by Na⁺,K⁺-ATPase (NKA). Being the single most important sink of energy, NKA might seem to be an essential target of the AMPK-mediated energy saving measures, yet NKA is vital for maintenance of transmembrane Na⁺ and K⁺ gradients, water homeostasis, cellular excitability, and the Na⁺-coupled transport of nutrients and ions. Consistent with the model that AMPK regulates ATP consumption by NKA, activation of AMPK in the lung alveolar cells stimulates endocytosis of NKA, thus suppressing the transepithelial ion transport and the absorption of the alveolar fluid. In skeletal muscles, contractions activate NKA, which opposes a rundown of transmembrane ion gradients, as well as AMPK, which plays an important role in adaptations to exercise. Inhibition of NKA in contracting skeletal muscle accentuates perturbations in ion concentrations and accelerates development of fatigue. However, different models suggest that AMPK does not inhibit or even stimulates NKA in skeletal muscle, which appears to contradict the idea that AMPK maintains the cellular energy balance by always suppressing ATP-consuming processes. In this short review, we examine the role of AMPK in regulation of NKA in skeletal muscle and discuss the apparent paradox of AMPK-stimulated ATP consumption.

AMP 活化蛋白激酶 (AMPK) 是细胞能量计和细胞能量稳态的主要调节器。一旦被激活，AMPK 会刺激营养吸收和产生 ATP 的分解代谢途径，同时抑制消耗 ATP 的合成代谢途径，从而有助于在能量缺乏条件下维持细胞能量平衡。由于 Na ⁺ ,K ⁺ -ATPase (NKA)催化的反应，导致全身 ATP 消耗的约 20-25% 发生。作为最重要的单一能量汇，NKA 似乎是 AMPK 介导的节能措施的基本目标，但 NKA 对于维持跨膜 Na ⁺和 K ⁺梯度、水稳态、细胞兴奋性和 Na ⁺- 营养物和离子的耦合运输。与 AMPK 通过 NKA 调节 ATP 消耗的模型一致，肺泡细胞中 AMPK 的激活刺激 NKA 的内吞作用，从而抑制跨上皮离子转运和肺泡液的吸收。在骨骼肌中，收缩会激活 NKA，它对抗跨膜离子梯度的下降，以及 AMPK，它在适应运动中起重要作用。收缩骨骼肌时 NKA 的抑制加剧了离子浓度的扰动并加速了疲劳的发展。然而，不同的模型表明 AMPK 不会抑制甚至刺激骨骼肌中的 NKA，这似乎与 AMPK 通过始终抑制 ATP 消耗过程来维持细胞能量平衡的观点相矛盾。在这篇简短的评论中，