Pathophysiological analysis of myocardial dysfunction by observing nanometer ordernanometer-order dynamics of actin-myosin, interaction

通过观察纳米级肌动蛋白-肌球蛋白的纳米级动力学、相互作用来分析心肌功能障碍

• 批准号: 17390231
• 负责人: SHIMIZU Juichiro
• 金额: $ 10.32万
• 依托单位: Nara Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390231/
• 关键词: SPring-8; X-ray Diffraction; Hypoxia; Myofilament Lattice; Crossbridge; Contraction; Frank Starling Law; Ca Transient; Heart Rate; Transmural Heterogeneity; X線回折; 心臓; 左心室自由壁; アクチン; ミオシン; クロスブリッジ; ラット

We have been proceeding to investigate into the cardiac physiology, especially in the myocardial excitation-contraction coupling. We study the cardiac performance in the isolated and in the in situ heart, theoretically analyze the data from the view of mechanoenergetics, and then speculate the myocardial intracellular Ca2+ dynamics and the myofilament crossbridge attach/detach kinetics. Then we found that the left ventricular myocardial intracellular Ca2+ dynamics is independent of the left ventricular volume and the left ventricular myofilament Ca2+ bound/unbound kinetics is also independent of the left ventricular volume. Then we proposed that the volume dependent increase in the cardiac contracting force that is known as Frank-Starling law is greatly dependent on the actin-myosin interaction. Several methods have been reported to investigate the actin-myosin interaction in variable level, most of them are the molecular level experiments. Tb investigate the myocardial actin-myosin in … More teraction in the physiologically contracting preparation, the x-ray diffraction technique is quite useful and reliable using synchrotron radiation. The x-ray provided by the first- and the second-generation synchrotron facilities were not enough strong to penetrate the myocardium and not enough monochromatic to make dear diffraction images. Because of these reasons, the investigators had to use thin papillary muscle and perform summation of diffraction images obtained from thousands of contractions to reduce S/N ratio. Now we can use the third generation synchrotron facility. Because the SPring-8 that is the world largest synchrotron facility can provide the ideal-ray characterized as 1) high photon flux, 2) monochromatic, and 3) collimated, we can analyze the actin-myosin interaction in the excised rat hearts in a single contraction without summation. We aimed to establish the x-ray diffraction analysis in isolated rat hearts and to analyze the relation between the left ventricular pressure and the actin-myosin interaction in the failing heart. The detailed results are in the main part of this report. Less

我们一直在进行心脏生理学的研究，特别是在心肌兴奋-收缩耦合方面。本文研究了离体心脏和在体心脏的心功能，从机械能学的角度对数据进行了理论分析，并推测了心肌细胞内Ca ~（2+）动力学和肌丝跨桥附着/分离动力学。结果发现，左心室心肌细胞内Ca ~（2+）动力学与左心室容积无关，左心室肌丝Ca ~（2+）结合/未结合动力学也与左心室容积无关。然后，我们提出，心脏收缩力的体积依赖性增加，被称为Frank-Starling定律，在很大程度上依赖于肌动蛋白-肌球蛋白相互作用。已有多种方法在不同水平上研究肌动蛋白-肌球蛋白相互作用，但大多数是分子水平的实验。探讨心肌肌动蛋白-肌球蛋白的变化 ...更多信息 在生理收缩制剂中，使用同步辐射的X射线衍射技术是非常有用和可靠的。第一代和第二代同步加速器设备提供的X射线强度不足以穿透心肌，单色性也不足以产生清晰的衍射图像。由于这些原因，研究人员不得不使用薄的乳头肌，并对从数千次收缩中获得的衍射图像进行求和，以降低S/N比。现在我们可以用第三代同步加速器了。由于SPring-8是世界上最大的同步辐射装置，可以提供1）高光子通量，2）单色，3）准直的理想射线，我们可以分析在一个单一的收缩在离体大鼠心脏肌动蛋白-肌球蛋白的相互作用，而无需求和。本研究旨在建立离体大鼠心脏的x射线衍射分析方法，并分析心力衰竭时左心室压力与肌动蛋白-肌球蛋白相互作用的关系。详细结果见本报告的主要部分。少

项目成果

Hypovolemia does not affect speed of isovolumic left ventricular contraction and relaxation in excised canine heart

低血容量不影响离体犬心脏等容左心室收缩和舒张的速度

• 发表时间: 2008
• 期刊: Shock (In press)
• 作者: Ju Mizuno;Juichiro Shimizu;Satoshi Mohri;Junichi Araki;Kazuo Hanaoka;and Yoshitsugu Yamada
• 通讯作者: and Yoshitsugu Yamada

Increasing preload attenuates crossbridge formation under hypoxia

增加预紧力会减弱缺氧条件下的横桥形成

Na^+/Ca^<2+> exchange inhibition protects the rat heart from ischemicreperfusion injury by blocking energy-wasting processes

Na^/Ca^<2>交换抑制通过阻断能量浪费过程保护大鼠心脏免受缺血再灌注损伤

• 发表时间: 2005
• 期刊: Am J Physiol Heart Circ Physiol 288
• 作者: Hirota M;Ishino K;Fukumasu I;Yoshida K;Mohri S;Shimizu J;Kajiya F;Sano S.;Miyamoto M;Miyazaki S;Nakahashi K;Hyodo T;Yoshikawa Y;Masahito Miyamoto;Xu Bo;Zhang Ying;Hagihara H
• 通讯作者: Hagihara H

シックハウス症候群関連化学物質ホルムアルデヒドの心機能に及ぼす影響

甲醛（一种与病态建筑综合症相关的化学物质）对心脏功能的影响

• 发表时间: 2007
• 作者: 竹下 大輔;清水 壽一郎;中島 千香子;高木 都
• 通讯作者: 高木 都

高い心拍数では心筋アクチンるミオシン架橋形成は減少する

在高心率下，心肌肌动蛋白之间的肌球蛋白交联形成减少。

• 发表时间: 2007
• 作者: Shimizu;J;清水 壽一郎
• 通讯作者: 清水 壽一郎