Comparison of putative cooperative mechanisms in cardiac muscle: length dependence and dynamic responses
Comparison of putative cooperative mechanisms in cardiac muscle: length dependence and dynamic responses
复制标题
DOI：
10.1152/ajpheart.1999.276.5.h1734
复制
发表时间：
1999-05-01
影响因子：
4.8
通讯作者：
Hunter, WC
中科院分区：
文献类型：
--
作者：
Rice, JJ;Winslow, RL;Hunter, WC
长度依赖性的稳态和动态响应的五个模型的等长力产生的心肌肌丝进行了比较，从文献中类似的实验数据。通过假设三种假定的合作机制的不同子集来构建模型。协同机制1认为跨桥结合增加了肌钙蛋白对Ca 2+的亲和力。在模型中，合作机制1可以产生陡峭的力-Ca ~（2+）（F-Ca）关系，但在中等Ca ~（2+）浓度下，表观合作性最高。在抽搐期间，协作机制1具有随着力的大小增加而增加峰值潜伏期的效果，这是实验上未观察到的效果。协同机制2认为，一个横桥的结合增加了相邻横桥的形成速率，并且多个横桥可以在不存在Ca 2+的情况下维持细丝的活化。只有合作机制2可以产生肌节长度（SL）依赖性的抽搐延长，但这种机制对稳态F-Ca关系的影响不大。协同机制3旨在模拟相邻肌钙蛋白和原肌球蛋白之间的端对端相互作用。这一机制可以产生陡峭的F-Ca关系，适当的SL依赖性变化的Ca 2+敏感性。假设原肌球蛋白移位比跨桥循环快，合作机制3产生抽搐，其中峰值潜伏期与力的大小无关，如实验所见。
Length-dependent steady-state and dynamic responses of five models of isometric force generation in cardiac myofilaments were compared with similar experimental data from the literature. The models were constructed by assuming different subsets of three putative cooperative mechanisms. Cooperative mechanism 1 holds that cross-bridge binding increases the affinity of troponin for Ca2+. In the models, cooperative mechanism 1 can produce steep force-Ca2+ (F-ca) relations, but apparent cooperativity is highest at midlevel Ca2+ concentrations. During twitches, cooperative mechanism 1 has the effect of increasing latency to peak as the magnitude of force increases, an effect not seen, experimentally. Cooperative mechanism 2 holds that the binding of a cross bridge increases the rate of formation of neighboring cross bridges and that multiple cross bridges can maintain activation of the thin filament in the absence of Ca2+. Only cooperative mechanism 2 can produce sarcomere length (SL)dependent prolongation of twitches, but this mechanism has little effect on steady-state F-Ca relations. Cooperativity mechanism 3 is designed to simulate end-to-end interactions between adjacent troponin and tropomyosin. This mechanism can produce steep F-Ca relations with appropriate SL-dependent changes in Ca2+ sensitivity. With the assumption that tropomyosin shifting is faster than cross-bridge cycling, cooperative mechanism 3 produces twitches where latency to peak is independent of the magnitude of force, as seen experimentally.