TIME-RESOLVED X-RAY DIFFRACTION OF CARDIAC MUSCLE

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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。本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Frank-Starling的细胞机制。为了探索这一假设，所提出的研究项目的目的是集中在回答以下问题，导致两个具体的目标：1）是丝间间距主动收缩前的生理相关参数，决定肌丝钙反应？一段时间以来，已知骨骼肌中的主动力发展与丝间间距的变化相关AIM 1：检验以下假设：活动肌肉中丝间间距随SL的变化是肌丝长度依赖性激活的基础;此外，在恒定SL的条件下确定晶格间距（LS）是否在激活期间变化，或者如通过恒定体积预测的那样保持恒定。目标二：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的舒张期，测试LS在肾上腺素能刺激期间的依赖性

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