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Morphological and ultrastructural changes of the membrane systems involved in excitation-contraction coupling in skeletal muscle during contraction

收缩过程中参与骨骼肌兴奋-收缩耦合的膜系统的形态和超微结构变化

基本信息

批准号：
11558003
负责人：
TAKEKURA Hiroaki
金额：
$ 8.58万
依托单位：
National Institute of Fitness and Sports in Kanoya
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

During excitation-contraction (e-c) coupling in skeletal muscle, depolarization of the surface membrane/transverse (T) tubule is converted into Ca^<2+> release from internal store, sarcoplasmic reticulum (SR). These two membrane systems make junctions with each other, named peripheral coupling, dyads, and triads or, collectively, calcium release units. Functional interaction between T tubule and SR involves two Ca^<2+> channels in these membrane complex: dihydropyridine receptors (DHPR) of surface membrane/transverse tubules, and ryanodine receptor (RyR) of SR. The steps leading to the differentiation of the specialized SR domain involved in CRUs are just beginning to be understood. Key to the formation of CRUs is a docking step, which allows the formation and stabilization of the SR-T tubule link. Candidates for the docking protein have been proposed. Another step is the insertion of RyRs and DHPRs within CRUs. The former can be followed using electron microscopy, since the cytoplasmic domains of RyRs are seen as well defined electron dense structures within the junctional gap between SR and plasmalemma/T tubules. Using the mouse diaphragm as a model, we report further insights into the morphogenesis of the membrane systems. We found that the SR-T docking and the trapping of RyRs at the junctions are two sequential steps in the formation of CRUs. A second, somewhat unexpected, finding is that the specific positioning of CRUs relative to the bands of the myofibrils proceeds positioning of the entire T tubule network in transverse planes associated with the myofibrils. We found that the SR-T docking and the trapping of RyRs at the junctions are two sequential steps in the formation of GRUs. These sequential stages suggest an order of inductive processes for the molecular differentiation and structural organization of the CRUs in skeletal muscle development.

在骨骼肌兴奋-收缩（e-c）偶联期间，表面膜/横（T）小管的去极化转化为来自内部储存肌浆网（SR）的Ca^<2+>释放。这两个膜系统相互连接，称为外周偶联、二联体和三联体，或者统称为钙释放单位。T小管和SR之间的功能性相互作用涉及这些膜复合物中的两个Ca^<2+>通道：表面膜/横小管的二氢吡啶受体（DHPR）和SR的兰尼碱受体（RyR）。导致CRU中所涉及的特化SR结构域分化的步骤才刚刚开始被理解。CRU形成的关键是对接步骤，其允许SR-T小管连接的形成和稳定。已经提出了对接蛋白的候选者。另一个步骤是在CRU中插入RyR和DHPR。前者可以使用电子显微镜进行观察，因为RyR的胞质结构域被视为SR和质膜/T小管之间的连接间隙内定义良好的电子致密结构。以小鼠横膈膜为模型，我们报告了膜系统的形态发生的进一步见解。我们发现SR-T对接和RyR在连接处的捕获是CRU形成的两个连续步骤。第二个有点出乎意料的发现是，CRU相对于肌原纤维带的特定定位使得整个T小管网络在与肌原纤维相关的横向平面中定位。我们发现SR-T对接和RyR在连接处的捕获是GRU形成的两个连续步骤。这些连续的阶段表明了骨骼肌发育中CRU分子分化和结构组织的诱导过程的顺序。