SKELETAL MUSCLE FATIGUE AND THE CONTRACTILE APPARATUS

骨骼肌疲劳和收缩装置

• 批准号: 2080945
• 负责人: Jay H. Williams
• 金额: $ 9.41万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-03-01 至 1998-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2080945
• 关键词: Rana; adenosinetriphosphatase; calcium flux; muscle cells; muscle contraction; muscle metabolism; muscle strength; striated muscles

Skeletal muscle fatigue has been defined as the inability of muscle to elicit a desired force output which it is normally capable of producing. The development of muscle fatigue affects a number of everyday activities including decreased exercise performance and worker productivity and is associated with increased susceptibility to orthopedic injury and precipitation of muscle soreness and damage. At present, the mechanisms which cause skeletal muscle fatigue are not fully understood. [It has recently been established that fatigue is associated with diminished maximal Ca2+ activated force and Ca2+ sensitivity of the contractile apparatus. Unfortunately, it is not clear if these changes are the direct result of fatiguing activity or are secondary to the accumulation of metabolic waste products (e.g. H+, P[i] and ADP). In addition, it is not clear if fatigue and/or its byproducts alter the relationship between force and Ca2+ by affecting the transitions of the cross-bridges to and from the force generating state (cross-bridge cycling kinetics) or by modulating cross-bridge recruitment and force generation. The experiments described in this proposal are designed to determine l) if fatigue directly alters maximal force production and Ca2+ sensitivity of the contractile apparatus and 2) if fatigue- and/or metabolite-induced changes in the relationship between force and free Ca2+ are due to altered cross- bridge cycling kinetics or to altered cross-bridge recruitment and/or their average force generation. This will be accomplished by examining cross-bridge recruitment, force generation and cycling kinetics in skinned skeletal muscle fibers taken from rested and fatigued muscles and exposed to incubation media that is formulated to mimic "rested" and "fatigued" intracellular environments. These parameters will be examined using measurements of the rate constant of force redevelopment after a period of isotonic shortening, complemented by measurements of isometric force, ATPase activity and stiffness during isometric contraction at various levels of free Ca2+. In general, the results of the proposed experiments will provide much needed information regarding the mechanisms of skeletal muscle fatigue. These findings should also lead to a better understanding of the fatigue process and provide an experimental basis for developing means of alleviating and avoiding muscle fatigue.]

骨骼肌疲劳已被定义为无法进行肌肉 引发通常能够产生的所需力输出。 肌肉疲劳的发展会影响许多日常活动 包括降低运动表现和工人的生产力，是 与增加对骨科损伤的易感性相关 肌肉酸痛和损害的降水。目前，机制 引起骨骼肌疲劳的原因尚不完全了解。 [有 最近确定疲劳与减少有关 收缩的最大Ca2+激活力和Ca2+灵敏度 设备。不幸的是，尚不清楚这些更改是否是直接的 疲劳活动的结果或继发于积累 代谢废物（例如H+，P [i]和ADP）。另外，不是 清楚疲劳和/或其副产品是否改变了 力和Ca2+通过影响交叉桥的过渡到和 从力量产生状态（跨桥骑自行车动力学）或 调节跨桥的招募和力产生。实验 本提案中描述的旨在确定l）如果疲劳 直接改变最大力的产生和Ca2+灵敏度 收缩设备和2）如果疲劳 - 和/或代谢物诱导的变化 在力和游离Ca2+之间的关系中，是由于交叉改变而引起的 桥梁骑自行车动力学或更改跨桥的招募和/或 他们的平均力产生。这将通过检查 皮肤中的杂交桥招募，力产生和循环动力学 从休息和疲劳的肌肉中取出的骨骼肌纤维并暴露 为模仿“休息”和“疲劳”的孵化培养基 细胞内环境。这些参数将使用 一段时间后的力速率常数的测量 等渗缩短，与等距力的测量相辅相成， 等距收缩期间的ATPase活性和刚度在各种 自由Ca2+的水平。通常，提出的实验结果 将提供有关骨骼机制的急需信息 肌肉疲劳。这些发现也应导致更好的理解 疲劳过程并为开发提供了实验基础 减轻和避免肌肉疲劳的手段。]