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。列出的机构适用于该中心，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。在细胞水平上，肌膜长度（SL）依赖性肌丝Ca2+灵敏度是这种现象（长度依赖性激活-LDA）的基础。尚不清楚如何通过肌肉的收缩仪传递有关SL的信息。我们研究的总体目标是阐明LDA构成的分子机制。由于我们最近发现，放松的肌肉中的丝间间距并不是LDA的基础，因此我们的第一个目的是检验以下假设：它是在LDA构成的活性肌肉中获得的丝间间距。其次，我们最近发现，肌钙蛋白，尤其是心脏肌钙蛋白L，在LDA中起关键作用。因此，在我们的第二个目标中，将决定肌细胞素和合作激活在肌丝长度依赖性激活中的作用。我们将检验以下假设：心脏肌钙蛋白足够和/或需要在条纹肌肉上赋予LDA。 X射线衍射和机械实验将使用皮肤肌肉中的重组蛋白提取 - 结构实验进行。尽管心脏的坦率坦率定律构成了心脏的基本特性，它在一个多世纪以来都受到赞赏，但仍未完全理解这种现象的分子机制。我们的研究计划旨在增强我们对这一重要生理过程的理解，该过程以节奏控制心脏表现。