Abstract：
Force generation in striated muscle is primarily controlled by structural changes in the actin-containing thin filaments triggered by an increase in intracellular calcium concentration. However, recent studies have elucidated a new class of regulatory mechanisms, based on the myosin-containing thick filament, that control the strength and speed of contraction by modulating the availability of myosin motors for the interaction with actin. This review summarizes the mechanisms of thin and thick filament activation that regulate the contractility of skeletal and cardiac muscle. A novel dual-filament paradigm of muscle regulation is emerging, in which the dynamics of force generation depends on the coordinated activation of thin and thick filaments. We highlight the interfilament signaling pathways based on titin and myosin-binding protein-C that couple thin and thick filament regulatory mechanisms. This dual-filament regulation mediates the length-dependent activation of cardiac muscle that underlies the control of the cardiac output in each heartbeat.
摘要：
横纹肌中的力产生主要受细胞内钙浓度增加引发的含肌动蛋白细丝的结构变化控制。然而,最近的研究阐明了一类新的调节机制，基于含有肌球蛋白的粗丝，通过调节肌球蛋白马达与肌动蛋白相互作用来控制收缩的强度和速度。本文综述了细细丝和粗丝激活调节骨骼肌和心肌收缩性的机制。一种新的肌肉调节的双丝范式正在出现，其中力产生的动力学取决于细丝和粗丝的协调激活。我们强调了基于肌动蛋白和肌球蛋白结合蛋白-C的丝间信号通路，它们耦合了纤细和粗丝的调节机制。这种双丝调节介导心肌的长度依赖性激活，这是每次心跳中控制心输出量的基础。预计《生理学年度回顾》的最终在线出版日期，第86卷是2024年2月。请参阅http://www。annualreviews.org/page/journal/pubdates的订正估计数。
