MYOCARDIAL SARCOMERE MECHANICS

心肌肌节力学

• 批准号: 3335660
• 负责人: GERALD H POLLACK
• 金额: $ 20.51万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-04-01 至 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3335660
• 关键词: Anura; biomechanics; heart contraction; heart disorder; laboratory rabbit; laboratory rat; lasers; mechanical pressure; molecular pathology; muscle tension; myofibrils; myosins; sarcomeres

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.

拟议的实验旨在继续探索动力学 心脏中的肌节 具体计划主要围绕 最近的一项发现：肌节比它们最初的长度缩短了1- 2 长度比肌节产生更多等长张力， 在整个收缩过程中保持其初始长度。 现象 被称为缩短导致的力量增强。 计划是 详细研究这一现象，探讨有关的几个假设 的基本机制，并确定影响，如果有， 心脏的收缩。 将使用三种准备课程，每种课程都有不同的级别 的组织。 在最高级别，单纤维和孤立的 将使用心脏小梁。 在下一层，肌节 动力学将在单个肌原纤维的水平上进行研究。 最后， 在最基本的水平上，将使用体外运动测定来研究 分子和细丝之间的相互作用。 这些活动的主要目的 多水平实验是为了确定是否机制在于 分子水平，或者更高的组织水平。 如果时间允许，第二个目标是学习更多的机械 这种独特的实验方法的结合现象。 的 能够探索众所周知的特征，如力-速度 长度-张力关系，等等，在纤维，肌原纤维， 而肌肉发达的水平提供了一个不寻常的机会， 这些特征背后的机制。