TIME-RESOLVED X-RAY DIFFRACTION OF CARDIAC MUSCLE

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。这项研究的总体目标是阐明肌丝长度依赖激活的结构机制(S)，这是导致Frank-Starling的细胞机制。为了探索这一假说，该研究项目的目标是回答以下两个具体目标的问题：1)主动收缩之前的肌丝间距是决定肌丝钙反应的生理相关参数吗？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距的变化有关目的1：检验激活肌肉中肌丝间距随SL的变化是肌丝长度依赖的激活的基础的假设；进一步确定在SL恒定的条件下，晶格间距(LS)是在激活过程中变化，还是像恒定体积所预测的那样保持恒定。目的：使用异丙肾上腺素，一种激活PKA磷酸化的化合物，已被证明在体内改变LS的舒张期，测试LS在肾上腺素能刺激过程中的依赖性

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