Joint Research on E-C coupling in Skeletal Muscle Cells

高等脊椎动物骨骼肌兴奋-收缩偶联（E-C偶联）的一个显著特征是收缩不需要Ca^<2+>内流。这是因为膜去极化直接触发肌浆网（SR）释放Ca^2+。本研究旨在揭示骨骼肌横管膜电-电偶联的信号转导机制。我们使用酶促分离的单肌管，其来自仅缺乏骨骼肌E-C偶联的肌肉发育不全的突变小鼠，并且发现硝苯地平，一种二氢吡啶（DHP）衍生物，对电荷运动没有明显影响，而在正常肌管中，硝苯地平使电荷运动减少约40%，表明电荷运动由DHP敏感和不敏感组分组成。我们还探索了动物进化的谱系树，发现骨骼肌E-C偶联出现在 关于我们 文昌鱼（Branchiostomalanceolatum）和七鳃鳗（Lampetra planeri）之间的较低的脊索动物。单快肌纤维的全细胞电压钳实验表明，这种进化的变化是伴随着膜内电荷运动，这是由硝苯地平，二氢吡啶（DHP）衍生物阻断的组件的外观。结果表明，E-C偶联的进化步骤伴随着DHP敏感电荷运动的出现，因此，DHP敏感电荷运动表达了DHP敏感电荷运动中的信号转导过程，表达了DHP受体分子响应膜去极化从SR释放Ca^2+的信号转导过程。目前的研究结果还表明，尽管人们认为这两者都是同一个DHP受体分子的功能，但DHP敏感的电荷运动与L型Ca^<2+>通道的动力学性质无关。因此，深入分析E-C偶联的分子基础，进一步阐明DHP受体分子的结构-功能关系，是目前亟待解决的问题。少

One distinctive feature of the excitation-contraction coupling (E-C coupling) of skeletal muscle in higher vertebrates is Ca^<2+>-influx is not necessary for contraction. This is because membrane depolarization directly triggers Ca^<2+> release from the sarcoplasmic reticulum (SR). The present international joint research was assigned to reveal the signal transduction mechanism in the skeletal muscle transverse tubular membrane underlying the E-C coupling. We used enzymatically dissociated single myotubes form mutant mice with muscular dysgenesis which lack only the skeletal muscle E-C coupling, and found that nifedipine, a dihydropyridine (DHP) derivative had no appreciable effect on the charge movement, whereas in normal myotubes, nifedipine decreased the charge movement by -40% indicting that the charge movement consists of DHP-sensitive and insensitive components. We also explored the genealogical tree of animal evolution, and found that the skeletal muscle E-C coupling appeared in … More lower chordates between amphioxus (Branchiostomalanceolatum) and lamprey (Lampetra planeri). Whole-cell voltage clamp experiments on single fast muscle fibres have revealed that this evolutionary change is accompanied by the appearance of a component of intramembrane charge movement, which is blocked by nifedipine, a dihydropyridine (DHP) derivative. The results reveal that the evolutionary step of the E-C coupling was accompanied by the appearance of DHP-sensitive charge movement, and hence.the DHP-sensitive charge movement expresses the signal transduction process in the DHP-sensitive charge movement expresses the signal transduction process in the DHP-receptor molecule to release Ca^<2+> from the SR in response to membrane depolarization. The present results have also revealed that the DHP-sensitive charge movement is independent of the kinetic properties of the L-type Ca^<2+> channel, although both are thought to be the function of the same DHP-receptor molecule. It becomes now an urgent forthcoming study to analyze the molecular bases of the evolutionary change in E-C coupling, which will make clearer the structural-functional relations of the DHP-receptor molecule. Less