TIME-RESOLVED X-RAY DIFFRACTION OF CARDIAC MUSCLE

心肌的时间分辨 X 射线衍射

• 批准号: 8168608
• 负责人: Pieter P. de TOMBE
• 金额: $ 1.44万
• 依托单位: ILLINOIS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168608
• 关键词: Adrenergic Agents; Cardiac Volume; Computer Retrieval of Information on Scientific Projects Database; Cyclic AMP-Dependent Protein Kinases; Dependence; Development; Filament; Funding; Goals; Grant; Heart; Institution; Isoproterenol; Length; Microfilaments; Muscle; Myocardium; Operating System; Phosphorylation; Research; Research Personnel; Research Project Grants; Resources; Skeletal Muscle; Source; Starling (law); Sturnus vulgaris; Testing; Time; United States National Institutes of Health; Variant; adrenergic; base; in vivo

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 overall goal of this research is to elucidate the structural mechanism(s) that underlie myofilament length dependent activation, the cellular mechanism responsible for Frank-Starling. To explore this hypothesis, the objective of the proposed research project is focused on answering the following questions that leads to two specific aims: 1) Is inter-filament spacing prior to active contraction the physiologically relevant parameter that determines myofilament Ca2+ responsiveness? It has been known for some time that active force development in skeletal muscle is associated with a change in inter-filament spacing AIM 1: to test the hypothesis that variation in inter-filament spacing with SL in active muscle underlies myofilament length dependent activation; furthermore determine under conditions of constant SL whether lattice spacing (LS) varies during activation, or remains constant as would be predicted by constant volume. Aim 2: Using isoproterenol, a compound that activates PKA phosphorylation, which has been shown to alter diastolic in vivo LS, test the dependence of LS during ¿-adrenergic stimulation

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 心脏的弗兰克-斯塔林定律描述了舒张末期容量和心脏射血量之间的相互关系，这是一种在逐次心跳基础上运行的调节系统。这项研究的总体目标是阐明肌丝长度依赖性激活的结构机制，即导致 Frank-Starling 的细胞机制。为了探索这一假设，拟议研究项目的目标集中于回答以下问题，从而实现两个具体目标：1）主动收缩之前的肌丝间间距是否是决定肌丝 Ca2+ 反应性的生理相关参数？一段时间以来，人们已经知道骨骼肌中主动力的发展与肌丝间间距的变化有关。目的1：检验主动肌中肌丝间间距随 SL 的变化是肌丝长度依赖性激活的基础这一假设；此外，确定在 SL 恒定的条件下，晶格间距 (LS) 在激活过程中是否变化，或者如通过恒定体积预测的那样保持恒定。目标 2：使用异丙肾上腺素（一种激活 PKA 磷酸化的化合物，已被证明可以改变体内 LS 舒张压），测试 LS 在 ¿-肾上腺素能刺激期间的依赖性