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Decomposition of activation process of skeletal muscle : potent acceleration of the rate-limiting step of contracting reaction by exogenously added active actin

骨骼肌激活过程的分解：通过外源添加活性肌动蛋白有效加速收缩反应的限速步骤

基本信息

批准号：
18500515
负责人：
UMAZUME Yoshiki
金额：
$ 2.05万
依托单位：
Jikei University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

Within the activation process of skeletal muscle decomposed into two steps : 1) the initiation of activation process induced by calcium-binding to regulatory proteins, and 2) the following self-regenerative activation process in which active contractile myosin heads recruit adjacent inactive myosin heads to contractile interaction with actin, it is likely that muscle fatigue hinders the latter self-regenerative process to reduce the maximal force and shortening velocity. Therefore, in the present study, we focused on the effect of the tension on the latter step using phosphate analog.The broad ^<19>F-NMR spectrum of the phosphate analog (AlFx) bound to myosin heads indicated that the analogs hardly exchange with the free AlFx in solution and the analog-bound myosin has little mobility in the sarcomeres. The X-ray diffraction pattern also indicated that the analog-bound myosin heads kept helically ordered arrangement around the thick filament backbone even at low temperature. The time c … More ourse of the analog release estimated from the recovery of initial rapid tension development of the fiber was the same as the change of the diffraction pattern suggesting that the rate-limiting step of the analog release is binding step of myosin to actin.The exogenous actin fragment activated the analog release significantly as expected, however, stretch activation was not observed for the acceleration exerted by exogenous actin fragment. Since exogenous actin fragment is free from sarcomere structure and does not bear strain generated by contractile myosin heads, the strain on thin filaments is considered to be necessary to enhance the self-regenerative activation process by stretch.Any of so far proposed mechanisms of muscle fatigue could not suppress contractility of skeletal muscle adequately. We consider that the self-regenerative process activated by actin binding with modulation through strain in thin filament synergistically amplifies the integrated suppressing effect beyond a simple summation. Less

骨骼肌内的激活过程分解为两个步骤：1）由钙结合到调节蛋白诱导的激活过程的启动，和2）随后的自我再生激活过程，其中活性收缩肌球蛋白头募集邻近的非活性肌球蛋白头以与肌动蛋白收缩相互作用，可能是肌肉疲劳阻碍了后一个自我再生过程以降低最大力和缩短速度。因此，在本研究中，我们重点研究了张力对磷酸盐类似物在后一步中的影响，<19>结合到肌球蛋白头上的磷酸盐类似物（AlFx）的宽~ 1F-NMR谱表明，类似物在溶液中几乎不与游离的AlFx交换，并且类似物结合的肌球蛋白在肌节中几乎没有移动性。X射线衍射图谱还表明，即使在低温下，类似物结合的肌球蛋白头仍保持螺旋有序排列在粗丝骨架周围。时间C ...更多信息从纤维的初始快速张力发展的恢复估计的类似物释放的过程与衍射图案的变化相同，这表明类似物释放的限速步骤是肌球蛋白与肌动蛋白的结合步骤，外源性肌动蛋白片段如预期的那样显著地激活类似物释放，但是没有观察到外源性肌动蛋白片段施加的加速的拉伸激活。由于外源性肌动蛋白片段不受肌节结构的影响，也不承受肌球蛋白头部收缩产生的应变，因此认为细丝上的应变是通过拉伸增强自我再生激活过程所必需的，目前提出的任何肌肉疲劳机制都不能充分抑制骨骼肌的收缩性。我们认为，激活肌动蛋白结合与调制通过应变细丝的自我再生过程协同放大的综合抑制作用超出了一个简单的总和。少