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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 心脏的坦率宣传法描述了末期舒适量和心脏弹出卷之间的相互关系，这是一种调节系统，以节拍为基础。基于这种现象的主要细胞机制是心肌丝丝对以更长的肌节长度（SL）激活Ca2+离子的反应性提高；这通常称为肌丝长度依赖性激活。在过去的十年中，统一的假设已得到接受，表明肌丝长度依赖性激活是由于SL的增加而厚至细丝分离的减少引起的，这反过来又被认为增加了跨桥形成的可能性。尽管其他人的较早实验数据支持了这一理论，但我们最近完成了一系列全面的实验，这些实验表明，放松的肌肉中丝间间距的变化不足以解释SL依赖性肌膜激活。因此，在肌肉中，仍然不知道有关SL有关的信息是如何通过收缩仪器传输的。因此，我们研究的总体目标是阐明肌丝长度依赖性激活的分子机制，为此，我们采用X射线衍射来了解拉伸过程中肌丝蛋白的结构相互作用，以及如何影响力产生。