TIME-RESOLVED X-RAY DIFFRACTION OF CARDIAC MUSCLE

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 所谓的“弗兰克 心脏的Starling定律”描述了舒张末期容积和心脏射血容积之间的关系，心脏射血容积是成人心脏中在逐搏基础上操作的主要调节系统。这种现象背后的主要细胞机制是心肌肌丝对较长肌节长度的激活Ca 2+离子的反应性增加。尽管各种研究小组进行了大量的实验研究，但导致反应性增加的基本机制仍然难以捉摸。本项目旨在确定这一现象背后的结构机制。 我们从电刺激，连续抽搐，大鼠心肌获得二维x射线衍射图案。我们特别感兴趣的是在舒张条件下肌肉长度的变化，可能与随后的力量产生的结构变化。 我们检查了头与细丝的相对位置（通过I11/I10赤道强度比），头从粗丝骨干中心的径向范围（从肌球蛋白层线），应变在粗丝骨干（根据m6子午线反射的间距），以及肌球蛋白头部围绕粗丝长轴法线的取向（m3反射强度）。如果这些因素作为肌节长度的函数而改变，则可以预期它们中的任何一个都会影响力的产生。

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.