MYOCARDIAL SARCOMERE MECHANICS

拟议中的实验旨在继续探索动力学 心脏中的肌节。具体计划很大程度上是围绕 一项最新发现：肌节缩短了最初的1-2% 长度比肌节产生的等长张力要大得多 在整个收缩过程中保持其初始长度。这一现象 已经被贴上了缩短诱导力量增强的标签。我们的计划是 详细研究这一现象，探索与之相关的几个假说 基本机制，并确定对 心脏的收缩。 将使用三个级别的准备，每个级别都不同 对组织的影响。在最高级别，单纤维和隔离 将使用心脏小梁。在下一层，萨科梅尔 动力学将在单个肌原纤维的水平上进行研究。最后， 在最基本的层面上，将使用体外运动试验来研究 分子和细丝之间的相互作用。这些活动的主要目的是 多水平实验是为了确定机制是否存在于 分子水平，或在更高的组织水平上。 在时间允许的情况下，第二个目标是学习额外的机械 通过这种独特的实验方法组合，我们发现了一些现象。这个 能够探索众所周知的特征，如力-速度 长度-张力关系等，在纤维-，肌原纤维-， 肌丝水平提供了一个不同寻常的机会来接近 这些功能背后的机制。

The proposed experiments are designed to continue to explore the dynamics of sarcomeres in the heart. The specific plans are built largely around a recent discovery: sarcomeres that shorten by 1-2% of their initial length generate substantially more isometric tension than sarcomeres that remain at their initial length throughout contraction. The phenomenon has been labelled shortening-induced force enhancement. The plan is to study the phenomenon in detail, to explore several hypotheses concerning the underlying mechanism, and to determine the impact, if any, on contraction of the heart. Three classes of preparation will be used, each at a different level of organization. At the highest level, single fibers and isolated cardiac trabeculae will be used. At the next level down, sarcomere dynamics will be studied at the level of the single myofibril. Finally, at the most basic level, an in vitro motility assay will be used to study interactions among molecules and filaments. The primary aim in these multi-level experiments is to determine whether the mechanism lies at the molecular level, or at some higher level of organization. Time permitting, a secondary goal is to study additional mechanical phenomena with this unique combination of experimental-approaches. The ability to explore well known features such as the force-velocity relation, the length-tension relation, etc., at the fiber-, myofibril-, and myofilament-level offers an unusual opportunity to approach the mechanisms underlying these features.