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

在骨骼肌的兴奋-收缩（e-c）耦合过程中，表面膜/横(T)小管的去极化转化为Ca^<2+>从内部储存肌浆网（SR）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，或统称为钙释放单位。T小管与SR之间的功能相互作用涉及这些膜复合物中的两个Ca^<2+>通道：表面膜/横管的二氢吡啶受体（DHPR）和SR的红嘌呤受体（RyR）。导致cru中涉及的特殊SR结构域分化的步骤才刚刚开始被理解。cru形成的关键是一个对接步骤，该步骤允许SR-T小管连接的形成和稳定。已经提出了对接蛋白的候选物。另一个步骤是在cru中插入ryr和dhpr。前者可以用电子显微镜观察，因为RyRs的细胞质结构域在SR和质膜/T小管之间的连接间隙内被视为定义良好的电子致密结构。使用小鼠隔膜作为模型，我们报告了对膜系统形态发生的进一步见解。我们发现SR-T的对接和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可以使整个T小管网络在与肌原纤维相关的横向平面上定位。我们发现SR-T的对接和ryr在连接处的捕获是gru形成的两个连续步骤。这些顺序的阶段提示了骨骼肌发育中cru分子分化和结构组织的诱导过程顺序。

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.