Acute exercise and digoxin effects on skeletal muscle Na+,K+ATPase regulation, K+ homeostasis and fatigue in humans:

这项资助研究的是骨骼肌中一种被称为钠钾泵的酶的调节，因为它的功能是将钾泵入细胞，并将钠泵出细胞。这种酶在肌肉收缩中至关重要，在支持我们的运动能力方面起着关键作用。我们的研究表明，急性运动会抑制这种酶的最大容量(活性)，从而使肌肉容易疲劳。我们检查一项明确的运动是否会导致疲劳，是否会抑制钠钾泵，以及运动后3小时内是否会恢复。钠钾泵由几种非常相似的酶组成，称为异构体，每一种都受一个单独的基因控制，具有略有不同的功能和调节。我们探索运动是否会导致调节这些异构体的基因被激活，以及这是否会导致肌肉细胞中异构体形成的增加。我们使用一种通常用于心力衰竭患者的药物，称为地高辛，它可以阻断钠钾泵的作用。在老鼠的肌肉中，这会降低肌肉表现，导致更早和更明显的疲劳。我们研究了在锻炼人体的肌肉中是否发生了类似的有害影响，并测量了其对肌肉钠和钾水平的影响。增加关于单次运动对肌肉影响的知识是重要的基础知识。这项研究将使人们对运动中钠钾泵的调节有了新的认识，从而加深我们对肌肉疲劳和运动基因反应的理解。了解运动的影响将有助于制定应对运动不足的策略，在澳大利亚，运动不足是健康的主要负担。通过改进药物使用和开发更具体的治疗方法，对地高辛作用的更好理解也将使心力衰竭患者受益。

This grant investigates the regulation of an enzyme in skeletal muscle referred to as the sodium-potassium pump, since its function is to pump potassium into the cell and sodium out of the cell. This enzyme is vital in enabling the muscles to contract and plays a key role in supporting our capacity to exercise. Our studies have suggested that acute exercise depresses the maximal capacity (activity) of this enzyme, thereby rendering the muscle liable to fatigue. We examine whether a well-defined exercise leading to fatigue, does inhibit the sodium-potassium pump and whether recovery occurs within 3 hours after exercise. The sodium-potassium pump is comprised of several variations of very similar enzymes, known as isoforms, each under the control of a separate gene and having slightly different functions and regulation. We explore whether exercise causes the genes regulating these isoforms to be activated and whether this results in an increased isoform formation in the muscle cell. We use a drug commonly used in patients with heart failure, called digoxin, which blocks the action of the sodium-potassium pump. In rat muscles this reduces muscular performance, with earlier and more pronounced fatigue. We examine whether a similar detrimental effect occurs in muscles of exercising humans and measure the resultant effects on muscle sodium and potassium levels. Increased knowledge about the effects of a single exercise bout on muscle is important fundamental knowledge. The study will lead to new knowledge about sodium-potassium pump regulation in exercising humans and thus enhance our understanding of muscle fatigue and gene responses to exercise. Understanding exercise effects will assist in development of strategies to counter physical inactivity, which is a major burden on health in Australia. Improved understanding of the actions of digoxin will also benefit patients with heart failure, through modified drug use and development of more specific treatment.