Institute of Vegetative Physiology, University of Cologne, Robert Koch Str 39, Cologne, Germany.
J Mol Cell Cardiol. 2010 May;48(5):843-50. doi: 10.1016/j.yjmcc.2009.12.020. Epub 2010 Jan 6.
The sarcomere is the core structure responsible for active mechanical heart function. It is formed primarily by myosin, actin, and titin filaments. Cyclic interactions occur between the cross-bridges of the myosin filaments and the actin filaments. The forces generated by these cyclic interactions provide the molecular basis for cardiac pressure, while the motion produced by these interactions provides the basis for ejection. The cross-bridge cycle is controlled by upstream mechanisms located in the membrane and by downstream mechanisms inside the sarcomere itself. These downstream mechanisms involve the Ca(2+)-controlled conformational change of the regulatory proteins troponin and tropomyosin and strong cooperative interactions between neighboring troponin-tropomyosin units along the actin filament. The kinetics of upstream and downstream processes have been measured in intact and demembranated myocardial preparations. This review outlines a conceptual model of the timing of these processes during the individual mechanical heart phases. Particular focus is given to kinetic data from studies on contraction-relaxation cycles under mechanical loads. Evidence is discussed that the dynamics of cardiac contraction and relaxation are determined mainly by sarcomeric downstream mechanisms, in particular by the kinetics of the cross-bridge cycle. The rate and extent of ventricular pressure development is essentially subjected to the mechanistic principles of cross-bridge action and its upstream and downstream regulation. Sarcomere relengthening during myocardial relaxation plays a key role in the rapid decay of ventricular pressure and in early diastolic filling.
肌节是负责心脏主动机械功能的核心结构。它主要由肌球蛋白、肌动蛋白和肌联蛋白丝组成。肌球蛋白丝的横桥与肌动蛋白丝之间发生循环相互作用。这些循环相互作用产生的力为心脏压力提供了分子基础，而这些相互作用产生的运动为射血提供了基础。横桥循环由位于膜上的上游机制和肌节本身内部的下游机制控制。这些下游机制涉及调节蛋白肌钙蛋白和原肌球蛋白的 Ca(2+) 控制构象变化，以及沿肌动蛋白丝相邻肌钙蛋白-原肌球蛋白单元之间的强协同相互作用。在完整的和去膜心肌制剂中已经测量了上游和下游过程的动力学。这篇综述概述了这些过程在单个机械心脏阶段的时间安排的概念模型。特别关注机械负荷下收缩-松弛循环研究中的动力学数据。讨论了证据表明，心脏收缩和松弛的动力学主要由肌节下游机制决定，特别是由横桥循环的动力学决定。心室压力发展的速度和程度主要受横桥作用及其上游和下游调节的力学原理控制。心肌松弛时肌节的再伸长在心室压力的快速衰减和早期舒张充盈中起着关键作用。
