Renaud Jean-Marc, Ørtenblad Niels, McKenna Michael J, Overgaard Kristian
Faculty of Medicine, Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Rd., Ottawa, ON, K1H 8M5, Canada.
Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark.
Eur J Appl Physiol. 2023 Nov;123(11):2345-2378. doi: 10.1007/s00421-023-05270-9. Epub 2023 Aug 16.
Perturbations in K have long been considered a key factor in skeletal muscle fatigue. However, the exercise-induced changes in K intra-to-extracellular gradient is by itself insufficiently large to be a major cause for the force decrease during fatigue unless combined to other ion gradient changes such as for Na. Whilst several studies described K-induced force depression at high extracellular [K] ([K]), others reported that small increases in [K] induced potentiation during submaximal activation frequencies, a finding that has mostly been ignored. There is evidence for decreased Cl ClC-1 channel activity at muscle activity onset, which may limit K-induced force depression, and large increases in ClC-1 channel activity during metabolic stress that may enhance K induced force depression. The ATP-sensitive K channel (K channel) is also activated during metabolic stress to lower sarcolemmal excitability. Taking into account all these findings, we propose a revised concept in which K has two physiological roles: (1) K-induced potentiation and (2) K-induced force depression. During low-moderate intensity muscle contractions, the K-induced force depression associated with increased [K] is prevented by concomitant decreased ClC-1 channel activity, allowing K-induced potentiation of sub-maximal tetanic contractions to dominate, thereby optimizing muscle performance. When ATP demand exceeds supply, creating metabolic stress, both K and ClC-1 channels are activated. K channels contribute to force reductions by lowering sarcolemmal generation of action potentials, whilst ClC-1 channel enhances the force-depressing effects of K, thereby triggering fatigue. The ultimate function of these changes is to preserve the remaining ATP to prevent damaging ATP depletion.
长期以来，钾离子（K）的扰动一直被认为是骨骼肌疲劳的关键因素。然而，运动引起的细胞内钾离子与细胞外钾离子梯度变化本身不够大，不足以成为疲劳期间力量下降的主要原因，除非与其他离子梯度变化（如钠离子的变化）相结合。虽然有几项研究描述了在高细胞外钾离子浓度（[K]）下钾离子诱导的力量抑制，但其他研究报告称，在次最大激活频率下，[K]的小幅增加会诱导增强作用，这一发现大多被忽视了。有证据表明，在肌肉活动开始时氯离子通道ClC-1的活性降低，这可能会限制钾离子诱导的力量抑制，而在代谢应激期间ClC-1通道活性大幅增加，这可能会增强钾离子诱导的力量抑制。ATP敏感性钾通道（K通道）在代谢应激期间也会被激活，以降低肌膜兴奋性。考虑到所有这些发现，我们提出了一个修订概念，即钾离子具有两种生理作用：（1）钾离子诱导的增强作用和（2）钾离子诱导的力量抑制。在低至中等强度的肌肉收缩过程中，与[K]增加相关的钾离子诱导的力量抑制被伴随的ClC-1通道活性降低所阻止，使得钾离子诱导的次最大强直收缩增强作用占主导，从而优化肌肉性能。当ATP需求超过供应，产生代谢应激时，钾离子通道和ClC-1通道都会被激活。钾离子通道通过降低肌膜动作电位的产生来导致力量下降，而ClC-1通道则增强钾离子的力量抑制作用，从而引发疲劳。这些变化的最终功能是保存剩余的ATP，以防止ATP耗尽造成损害。
