Skeletal muscle ion and volume regulation at rest, during contraction and recovery

休息时、收缩和恢复期间的骨骼肌离子和体积调节

• 批准号: 36641-2009
• 负责人: Lindinger, Michael
• 金额: $ 2.02万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=504104
• 关键词: Skeletal; muscle; ion; volume; regulation

My research continues to examine mechanisms of regulating ion and fluid balance in skeletal muscle and in intact mammals. The long-term objectives are to increase the basic knowledge and understanding of the processes affecting skeletal muscle function and whole body performance during activity and recovery from activity. The short-term objectives are to: 1) continue to study the function and regulation of the skeletal muscle sodium-potassium-chloride cotransporter (NKCC); 2) to begin to study mechanisms of regulating Na,K pump activity in skeletal muscle cells recovering from contractile activity; and 3) examine the influence of high intensity exercise on muscle potassium transport pathways during both the contractile period and during recovery. We use two main experimental approaches in an integrated manner that spans from molecular to the tissue level. The first approach uses an intact isolated rat hindlimb preparation that is perfused with an artificial blood of known and constant composition. The strength of this approach is that it permits the determination of net and unidirectional ion, metabolite and fluid fluxes between vascular and muscle compartments, together with measurements of ion and metabolite changes within the stratified fiber type population of the lower rat hindlimb. The conditions closely approximate those found in vivo, yet confer the benefits of increased control of perfusate composition and the experimental paradigm. The second approach uses mouse skeletal muscle bundles or single fibres studied in vitro to determine the time course of change in intracellular ion status, membrane potential and cell volume in response hypertonic stress, ion transport activators and ion transport inhibitors. This work is expected to improve our understanding of skeletal muscle and whole animal ion and fluid regulation during rest, exercise, fatigue and recovery. It is further expected that the results will transfer to the study of muscle pathologies involving electrolyte, contractile and metabolic imbalances such as muscular dystrophy and type II diabetes.

我的研究继续研究骨骼肌和完整哺乳动物中离子和液体平衡的调节机制。长期目标是增加对活动和活动恢复期间影响骨骼肌功能和全身表现的过程的基本知识和理解。近期目标是：1）继续研究骨骼肌钠-钾-氯协同转运蛋白（NKCC）的功能和调节; 2）开始研究骨骼肌细胞从收缩活动恢复中Na，K泵活性的调节机制; 3）检查高强度运动对收缩期和恢复期肌肉钾转运途径的影响。我们使用两个主要的实验方法，在一个综合的方式，从分子到组织水平的跨度。第一种方法使用一个完整的离体大鼠后肢制备灌注与人工血液的已知和恒定的组成。这种方法的优点是，它允许确定净和单向离子，代谢物和流体之间的血管和肌肉室的流量，以及测量离子和代谢物的变化内的分层纤维型人口的大鼠后肢。这些条件与体内发现的条件非常接近，但赋予了增加灌注液组成和实验范例的控制的益处。第二种方法使用小鼠骨骼肌束或单纤维在体外研究，以确定细胞内离子状态，膜电位和细胞体积的变化，在响应高渗应力，离子转运激活剂和离子转运抑制剂的时间过程。这项工作有望提高我们对骨骼肌和整个动物在休息、运动、疲劳和恢复过程中离子和液体调节的理解。进一步预计，结果将转移到涉及电解质，收缩和代谢失衡的肌肉病理学研究，如肌肉萎缩症和II型糖尿病。