TIME-RESOLVED X-RAY DIFFRACTION OF CARDIAC MUSCLE

心肌的时间分辨 X 射线衍射

• 批准号: 7369132
• 负责人: Pieter P. de TOMBE
• 金额: $ 0.89万
• 依托单位: ILLINOIS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7369132
• 关键词: TIME; RESOLVED; RAY; DIFFRACTION; CARDIAC

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. At the cellular level, sarcomere length (SL) dependent myofilament Ca2+ sensitivity underlies this phenomenon (length dependent activation-LDA). How information concerning SL is transduced by the contractile apparatus of muscle is not known. The overall goal of our research is to elucidate the molecular mechanisms that underlie LDA. Since we have recently found that inter-filament spacing in a relaxed muscle does not underlie LDA our first aim is to test the hypothesis that it is inter-filament spacing attained in an active muscle that underlies LDA. Secondly, we have recently found that troponin, and particularly cardiac troponin-l, plays a pivotal role in LDA. Therefore, in our second aim will determine the role of troponin and cooperative activation in myofilament length dependent activation. We will test the hypothesis that cardiac troponin is sufficient and/or required to impart LDA upon a striated muscle; combined X-ray diffraction and mechanical experiments will be performed using recombinant protein extraction-reconstitution experiments in skinned muscle. Although the Frank-Starling Law of the Heart constitutes a fundamental property of the heart that has been appreciated for well over a century, the molecular mechanisms that underlie this phenomenon are still incompletely understood. Our research plan is aimed to enhance our understanding of this important physiological process that controls cardiac performance on a beat to beat basis.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。心脏的Frank-Starling定律描述了舒张末期容积和心脏射血容积之间的相互关系，这是一种在逐搏基础上运行的调节系统。在细胞水平上，肌节长度（SL）依赖性肌丝Ca 2+敏感性是这种现象（长度依赖性激活-LDA）的基础。关于SL的信息是如何通过肌肉的收缩器官进行传递的，目前还不清楚。我们研究的总体目标是阐明LDA的分子机制。由于我们最近发现，在一个放松的肌肉中的细丝间的间距并不构成LDA的基础，我们的第一个目标是测试的假设，这是在一个活跃的肌肉中获得的细丝间的间距，构成LDA的基础。其次，我们最近发现肌钙蛋白，特别是心肌肌钙蛋白-I，在LDA中起着关键作用。因此，我们的第二个目标是确定肌钙蛋白和协同激活在肌丝长度依赖性激活中的作用。我们将检验心肌肌钙蛋白足以和/或需要在横纹肌上赋予LDA的假设;将在带皮肌肉中使用重组蛋白提取-重构实验进行组合X射线衍射和机械实验。尽管心脏的Frank-Starling定律构成了心脏的基本性质，并且已经被认识了超过世纪，但是这种现象背后的分子机制仍然没有完全理解。我们的研究计划旨在提高我们对这一重要生理过程的理解，这一过程控制着心脏的跳动。