Role of nitric oxide and reactive oxygen species in excitation-contraction coupling in skeletal muscle.

兴奋-收缩（E-C）耦合是一个用于广泛描述细胞事件序列的术语，从肌细胞表面膜上的电信号开始，然后最终导致肌肉收缩。虽然整个序列是已知的，但我们对正常肌肉功能以及过度运动和疾病如何损害这种功能的机制的理解仍有许多空白。许多细胞代谢物有助于肌肉收缩的正常控制，而其他代谢物则有助于肌肉收缩的损伤。活性氧（ROS）包括一氧化氮（NO）及其相关分子，是一种代谢因子，通常被称为细胞氧化剂。它们被认为在控制正常肌肉功能方面起着至关重要的作用。矛盾的是，它们还与疲劳、疾病和衰老相关的肌肉功能损伤有关。这些分子是如何既控制正常的肌肉活动，又导致这些功能受损的，目前还不清楚。因此，该项目的中心目标是确定细胞氧化剂NO和其他ROS控制骨骼肌纤维中正常E-C偶联的机制，以及它们如何导致肌肉疲劳。显然，了解骨骼肌如何正常收缩是必不可少的，以便更好地了解肌肉功能如何随着运动、疾病和年龄而受损。这项研究的工作将为正常肌肉生理学和肌肉疲劳提供见解，并最终提供新的方法和药物，以对抗疲劳、疾病和与年龄相关的肌肉功能变化。

Excitation-contraction (E-C) coupling is a term used to broadly describe the sequence of cellular events that starts with an electrical signal at the surface membrane of a muscle cell and which then ultimately leads to muscle contraction. Although the overall sequence is known, there remain many gaps in our understanding of the mechanisms involved not only related to normal muscle function but to how this function may be impaired by excessive exercise and disease. Many cellular metabolites contribute towards the normal control of muscle contraction, while others contribute to its impairment. Reactive oxygen species (ROS), which includes nitric oxide (NO) and related molecules, are metabolic factors often referred to as cellular oxidants. They are thought to have an essential role in controlling normal muscle function. Paradoxically, they are also implicated in the impairment of muscle function associated with fatigue, disease and aging. How these molecules both control normal muscle activity and also contribute to impairment of such function remains unclear. Thus, the central aim of this project is to identify the mechanisms by which the cellular oxidants, NO and other ROS, both control normal E-C coupling in skeletal muscle fibres and how they contribute to muscle fatigue. Clearly, understanding how skeletal muscle normally contracts is essential in order to better understand how muscle function can become impaired with exercise, disease and age. The work from this study will provide insight into both normal muscle physiology and how muscles fatigue and ultimately provide new methodologies and drugs that may combat fatigue, disease and age related changes to muscle function.