MYOCARDIAL SARCOMERE MECHANICS

这项研究的目的是揭示某些特定事件背后的机制 心脏力学的基本特征。为了做到这一点，我们将进行 在三个层次级别中的每一个级别进行平行实验 组织：分离的小梁，分离的单个肌原纤维，以及 孤立的肌丝。第一个涉及到一种用于 实验室里待了一段时间。离体心肌节力学 小梁的研究具有很高的空间和时间分辨率。 第二种是单个分离的肌原纤维，是最近开发的一种制剂。 发展起来的。它的优点是在准备过程中每个肌节 可以观察到，由于肌节是连续的，张力 任何给定的肌节所产生的肌节是在 样本。因此，可以建立每个肌节的机制。 毫不含糊。第三种制剂是体外运动试验，在 荧光标记的肌动蛋白细丝的运动可以是 在种植在基质上的肌球蛋白头的草坪上观察。通过 速度、张力和细丝力学的联合测量 可以被建立起来。通过同时使用这三种制剂 实验，将有可能剖析潜在的基本机制 力学的特点。我们计划研究长度-张力关系， 停用、增强张力、拉伸效果及其他相关因素 机械现象。通过观察某一现象是否出现 在一定的结构组织水平上，将有可能 迅速排除某些假定的机制。然后我们可能会更专注于 强烈地攻击其他人。探索力学现象的能力 同一实验室的三个层次的组织应允许快速 了解心脏收缩的基本原理的进展。

The aim of this research is to uncover the mechanisms underlying certain basic features of cardiac mechanics. To do so, we will carry out parallel experiments at each of three hierarchical levels of organization: isolated trabeculae, isolated single myofibrils, and isolated myofilaments. The first involves a preparation used in this laboratory for some time. Sarcomere mechanics of isolated cardiac trabeculae can be investigated with high spatial and temporal resolution. The second, single isolated myofibrils, is a preparation recently developed. It has the advantage that every sarcomere in the preparation can be observed, and since sarcomeres are in series, the tension generated by any given sarcomere is that measured at the end of the specimen. Thus, the mechanics of each sarcomere can be established unambiguously. The third preparation is the in vitro motility assay, in which the motion of fluorescently labelled actin filaments can be observed over a lawn of myosin heads planted on a substrate. By combining measurements of velocity and tension, mechanics of filaments can be established. By using these three preparations in parallel experiments, it will be possible to dissect mechanisms underlying basic features of mechanics. We plan to study length-tension relations, deactivation, tension-enhancement, effect of stretch, and other pertinent mechanical phenomena. By observing whether or not a phenomenon shows up at a certain level of structural organization, it will be possible to swiftly rule out certain putative mechanisms. We may then focus more intensely on others. The ability to explore mechanical phenomena at three levels of organization in the same laboratory should permit rapid advance in understanding of the basic principles of cardiac contraction.