STRUCTURE OF TRIAD JUNCTION: MUSCLE CONTRACTION

(支持NIH/NCRR/P-41 RR 01219和NIH AR40615至T. 瓦根克内赫特)。在骨骼肌和心肌中， 肌肉收缩发生在称为三联体的亚细胞结构上。 交汇点。三合会详细的三维结构 结点将有助于更好地理解分子 肌肉收缩的基础。这种理解最终可能会导致 改善对影响肌肉的疾病的治疗 收缩过程。在骨骼肌中，这些疾病包括 恶性高热、中枢性核心病和低钾周期性 瘫痪。目前用于治疗心脏疾病的许多药物 疾病被认为通过作用于 三合一结合部的组件。了解系统的结构 三联体连接是设计高效心脏药物的关键 疾病。青蛙肌肉三联体的结构正在被 钙离子释放通道位置的研究 与T管和肌浆网的关系。这是 补充钙释放通道的重建 在瓦根克内希特博士的团队中使用单粒子 接近。在BMIRR赠款提案中，三合会交界处是 被指定为三个对象之一(其他对象是 线粒体和初级纤毛)，用于 自动层析成像系统的开发和测试。在 上一次报告所述期间，黑社会的四次双倾斜重建 高压冷冻、冷冻替代的青蛙缝纫肌的连接 肌肉由0.18(M)m塑料切片制成，使用IVEM。一个 重建也是由冷冻水合制剂进行的 孤立的三合一交汇点。这项工作在几次会议上得到了报告。 在本报告所述期间，以前获得的倾斜系列数据 并使用重建来测试不同的加权方案 3-D重建和“小波”去噪的有效性 技术(见TRD“小波在图像降噪中的应用 从旧的倾斜系列图像进行新的重建 通过加权反投影法，使用加权 任意倾斜几何的函数(M.Radermacher(1992)加权 反投影法。收录于：电子断层摄影术，编辑，J·弗兰克， 全会，纽约)。这些都被与用 R加权反投影法。重建工作是用 并且没有基于小波的去噪技术。现在的结果是 正在被分析。

(Support NIH/NCRR/P-41 RR 01219 and NIH AR40615 to T. Wagenknecht). In both skeletal and heart muscles, the key events of muscle contraction occur at subcellular structures known as triad junctions. The detailed three-dimensional architecture of the triad junction will contribute to better understanding of the molecular basis of muscle contraction. This understanding may ultimately lead to improved treatments for diseases that affect the muscular contraction process. In skeletal muscle, these diseases include malignant hyperthermia, central core disease, and hypokalemic periodic paralysis. Many of the drugs that are currently used to treat heart disease are believed to produce therapeutic effects by acting on components of the triad junction. Understanding the structure of the triad junction is critical to design highly effective drugs for heart diseases. The structure of the frog muscle triad junction is being studied to investigate the site of the calcium release channel in relation to the t-tubes and sarcoplasmic reticulum. This is complementary to the reconstructions of the calcium release channel being done in Dr. Wagenknecht's group using the single-particle approach. In the BMIRR grant proposal, the triad junction was designated as one of the three objects (the others were the mitochondrion and the primary cilium) which would be used for development and testing of the automated tomography system. In the previous reporting period, four double-tilt reconstructions of triad junctions from high-pressure frozen, freeze-substituted frog sartorius muscle were made from 0.18(m plastic sections, using the IVEM. A reconstruction was also made from a frozen-hydrated preparation of isolated triad junctions. The work was reported at several meetings. During this reporting period, the previously obtained tilt-series data and reconstructions were used to test different weighting schemes for 3-D reconstruction, and the usefulness of "wavelet" denoising techniques (see TRD "Use of wavelets for noise reduction of images for tomography"). New reconstructions from the old tilt-series images were made by the weighted back-projection method, using a weighting function for arbitrary tilt geometry (M. Radermacher (1992) Weighted back-projection methods. In: Electron Tomography, Ed., J Frank, Plenum, New York). These were compared to reconstructions made with the R-weighted back-projection method. Reconstructions were made with and without wavelet-based denoising techniques. The results are now being analyzed.