Models of calcium activation account for differences between skeletal and cardiac force redevelopment kinetics
Models of calcium activation account for differences between skeletal and cardiac force redevelopment kinetics
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DOI：
10.1023/a:1018635907091
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发表时间：
1997-12-01
影响因子：
2.7
通讯作者：
Gordon, AM
中科院分区：
文献类型：
--
作者：
Hancock, WO;Huntsman, LL;Gordon, AM
为了解释所观察到的差异，心脏和骨骼肌之间的力重建动力学的激活依赖性，两个数值模型的收缩调节Ca2+进行了研究。Ca2+结合和力的产生分别建模为两个状态的过程与正向和反向速率常数取自文献。第一个模型包括四种可能的细丝状态。在第二个模型中，假设Ca 2+在力产生状态下不从细丝单元解离，从而导致三种状态。四态模型可以解释骨骼肌中张力重建速率常数（k（tr））的激活依赖性，而不需要Ca2+直接调节跨桥循环中任何步骤的动力学。使用相同的动力学参数，三态模型显示没有激活依赖性的k（tr），与我们在心肌中的结果一致。在[Ca2+]逐步增加后，两种模型的张力升高速率（如速率常数k（Ca）所述）随最终[Ca2+]而变化，与骨骼肌和心肌的实验结果一致。这些数值模型表明，实验测量认为，揭示动力学参数的变化可能只是反映了两个动力学过程的钙离子结合和力的产生之间的耦合。此外，该模型提出了可能的差异，在心脏和骨骼肌之间的钙激活方案，这可以解释力重建动力学的对比激活依赖性。
To explain observed differences in the activation dependence of force redevelopment kinetics between cardiac and skeletal muscle, two numerical models of contractile regulation by Ca2+ were investigated. Ca2+ binding and force production were each modelled as two-state processes with forward and reverse rate constants taken from the literature. The first model incorporates four possible thin-filament states. In the second model Ca2+ is assumed not to dissociate from a thin-filament unit in the force-generating state, resulting in three states. The four-state model can account for the activation dependence of the rate constant of tension redevelopment (k(tr)) seen in skeletal muscle, without requiring that Ca2+ directly modulates the kinetics of any step in the cross-bridge cycle. Using identical kinetic parameters, the three-state model shows no activation dependence of k(tr), consistent with our results in cardiac muscle. Following a step increase in [Ca2+], the rate of rise in tension (as described by the rate constant k(Ca)) varies with the final [Ca2+] for both models, consistent with experimental results from skeletal and cardiac muscle. These numerical models demonstrate that experimental measurements thought to reveal changes in kinetic parameters may simply reflect coupling between the two kinetic processes of Ca2+ binding and force generation. Furthermore, the models present possible differences in the Ca2+ activation scheme between cardiac and skeletal muscle which can account for the contrasting activation dependencies of force redevelopment kinetics.