TIME-RESOLVED X-RAY DIFFRACTION OF CARDIAC MUSCLE

心肌的时间分辨 X 射线衍射

• 批准号: 7722741
• 负责人: Pieter P. de TOMBE
• 金额: $ 5.06万
• 依托单位: ILLINOIS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7722741
• 关键词: Cardiac; Cardiac Volume; Computer Retrieval of Information on Scientific Projects Database; Data; Filament; Funding; Goals; Grant; Heart; Institution; Ions; Length; Microfilaments; Molecular; Muscle; Myocardium; Operating System; Probability; Production; Proteins; Research; Research Personnel; Resources; Sarcomeres; Series; Source; Starling (law); Stretching; Thick; Thin Filament; Time; United States National Institutes of Health; Variant; X ray diffraction analysis; X-Ray Diffraction; base; research study; theories

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Frank-Starling law of the heart describes the interrelationship between end-diastolic volume and cardiac ejection volume, a regulatory system that operates on a beat to beat basis. The main cellular mechanism that underlies this phenomenon is an increase in the responsiveness of cardiac myofilaments to activating Ca2+ ions at a longer sarcomere length (SL); this is commonly referred to as myofilament length dependent activation. Over the past decade a unifying hypothesis has gained acceptance stating that myofilament length dependent activation is caused by the reduction in thick to thin filament separation upon an increase in SL which, in turn, is hypothesized to increase the probability of cross-bridge formation. Although earlier experimental data by others supported this theory, we have recently completed a comprehensive series of experiments that show that variation of inter-filament spacing in a relaxed muscle is not sufficient to explain SL dependent myofilament activation. Hence, it is still not known in muscle how the information concerning SL is transduced by the contractile apparatus. Accordingly, the overall goal of our research is to elucidate the molecular mechanism(s) that underlie myofilament length dependent activation, to that end we employ X-ray diffraction to understand the structural interaction of myofilament proteins during stretch and how that might impact force production.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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相互关系，这是一种在逐个心跳的基础上运行的调节系统。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(SL)的钙离子激活的反应性增加；这通常被称为肌丝长度依赖的激活。在过去的十年中，一个统一的假说得到了人们的认可，该假说表明，肌丝长度依赖的激活是由于SL增加而导致粗细丝分离的减少，这反过来又假设增加了跨桥形成的可能性。尽管其他人的早期实验数据支持这一理论，但我们最近完成了一系列全面的实验，表明松弛肌肉中肌丝间距的变化不足以解释SL依赖的肌丝激活。因此，在肌肉中，关于SL的信息是如何通过收缩装置进行转导的，目前还不清楚。因此，我们研究的总体目标是阐明肌丝长度依赖激活的分子机制(S)，为此，我们使用X射线衍射来了解肌丝蛋白在拉伸过程中的结构相互作用以及这可能如何影响力的产生。