TIME-RESOLVED X-RAY DIFFRACTION OF CARDIAC MUSCLE

心肌的时间分辨 X 射线衍射

• 批准号: 8361264
• 负责人: Pieter P. de TOMBE
• 金额: $ 2.97万
• 依托单位: ILLINOIS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361264
• 关键词: Adult; Affect; Biophysics; Cardiac; Cardiac Volume; Funding; Grant; Head; Heart; Ions; Length; Microfilaments; Muscle; Myocardium; Myosin ATPase; National Center for Research Resources; Operating System; Pattern; Positioning Attribute; Principal Investigator; Production; Radial; Rattus; Relative (related person); Research; Research Infrastructure; Resources; Sarcomeres; Source; Starling (law); Thick Filament; Thin Filament; Time; United States National Institutes of Health; Vertebral column; X ray diffraction analysis; X-Ray Diffraction; base; cost; interest; two-dimensional

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The so-called "Frank Starling Law of the Heart" describes the relationship between end-diastolic volume and cardiac ejection volume that is the major regulatory system operating on a beat to beat basis in the adult heart. The main cellular mechanism that underlies this phenomenon is an increase in the responsiveness of cardiac myofilaments to activating Ca2+ ions at longer sarcomere lengths. The fundamental mechanism responsible for this increase in responsiveness has been elusive despite considerable experimental scrutiny by various research groups. This project we aim to determine the structural mechanisms behind this phenomenon. We obtain two-dimensional x-ray diffraction patterns from electrically stimulated, continuously twitching, rat cardiac muscle . We are particularly interested in structural changes that occur with changes in muscle length under diastolic conditions that can be related to subsequent force production. We examine the relative position of the heads to the thin filaments (via the I11/I10 equatorial intensity ratio), the radial extent of the heads from the center of the thick filament backbones (from the myosin layer lines), strain in the thick filament backbones (from the spacing of the m6 meridional reflection), and the orientation of the myosin heads around the normal to the thick filament long axis (m3 reflection intensity). Any of these factors could be expected to affect force production if they change as a function of sarcomere length.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 所谓的“弗兰克·斯塔林心脏定律”描述了舒张末期容量和心脏射血量之间的关系，这是成年人心脏的主要调节系统，以逐跳为基础进行操作。这一现象背后的主要细胞机制是心肌肌丝对较长肌节长度的钙离子激活的反应性增加。尽管不同的研究小组进行了大量的实验审查，但导致响应性增加的基本机制一直难以捉摸。这个项目我们的目标是确定这种现象背后的结构机制。我们从电刺激、持续抽动的大鼠心肌中获得了二维X射线衍射图。我们特别感兴趣的是，在舒张期条件下，随着肌肉长度的变化而发生的结构变化，这可能与随后的力量产生有关。我们检查了头部与细丝的相对位置(通过I11/I10赤道强度比)，头部从粗丝脊骨中心的径向范围(来自肌球蛋白层线)，粗丝脊骨中的应变(从M6经向反射的间距)，以及肌球蛋白头围绕法线到粗丝长轴的方向(M3反射强度)。如果这些因素随着肌节长度的变化而变化，那么这些因素中的任何一个都有望影响力量的产生。