Dynamic coupling of regulated binding sites and cycling myosin heads in striated muscle
Dynamic coupling of regulated binding sites and cycling myosin heads in striated muscle
复制标题
DOI：
10.1085/jgp.201311078
复制
发表时间：
2014-03-01
影响因子：
3.8
通讯作者：
Campbell, Kenneth S.
中科院分区：
文献类型：
--
作者：
Campbell, Kenneth S.
在激活的肌肉中，细丝和肌凝蛋白头部的结合位点经常在不同状态之间切换。由于结合位点的状态影响头的状态，反之亦然，结合位点和肌凝蛋白头是动态耦合的。使用一种新的肌肉计算机模型MyoSim研究了这种耦合的功能后果。MyoSim扩展了现有的基于赫胥黎分布技术的模型，结合了Ca2+激活和协同效应。它还可以模拟研究者设定的任意过桥方案。最初的计算研究了改变结合位点和过桥动力学的相对速度以及操纵协同过程的影响。随后的测试将模拟力记录与使用渗透心肌制剂记录的实验数据相匹配。这些计算表明，在最大激活状态下的力发展速率受肌球蛋白循环动力学的限制，而在较低激活水平下的力发展速率受结合位点可用速度的限制。额外的测试通过实验记录的Ca2+信号驱动模拟来研究瞬态激活细胞的行为。一个抽动的肌细胞的空载缩短轮廓可以用两种肌球蛋白状态、协同激活和菌株依赖动力学模型再现。总的来说，这些结果表明结合位点和肌凝蛋白头部的动态耦合对于收缩功能是重要的。
In an activated muscle, binding sites on the thin filament and myosin heads switch frequently between different states. Because the status of the binding sites influences the status of the heads, and vice versa, the binding sites and myosin heads are dynamically coupled. The functional consequences of this coupling were investigated using MyoSim, a new computer model of muscle. MyoSim extends existing models based on Huxley-type distribution techniques by incorporating Ca2+ activation and cooperative effects. It can also simulate arbitrary cross-bridge schemes set by the researcher. Initial calculations investigated the effects of altering the relative speeds of binding-site and cross-bridge kinetics, and of manipulating cooperative processes. Subsequent tests fitted simulated force records to experimental data recorded using permeabilized myocardial preparations. These calculations suggest that the rate of force development at maximum activation is limited by myosin cycling kinetics, whereas the rate at lower levels of activation is limited by how quickly binding sites become available. Additional tests investigated the behavior of transiently activated cells by driving simulations with experimentally recorded Ca2+ signals. The unloaded shortening profile of a twitching myocyte could be reproduced using a model with two myosin states, cooperative activation, and strain-dependent kinetics. Collectively, these results demonstrate that dynamic coupling of binding sites and myosin heads is important for contractile function.