Nonlinear dynamics of cardiac excitation-contraction coupling: An iterated map study
Nonlinear dynamics of cardiac excitation-contraction coupling: An iterated map study
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DOI：
10.1103/physreve.75.011927
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发表时间：
2007-01-01
影响因子：
2.4
通讯作者：
Weiss, James N.
中科院分区：
文献类型：
--
作者：
Qu, Zhilin;Shiferaw, Yohannes;Weiss, James N.
心肌细胞是可兴奋细胞，其中外部电流刺激使膜电位去极化以引起动作电位。然后，该动作电位触发细胞内储存的钙释放，这介导收缩。相反，细胞内钙也调节膜电流，影响动作电位形态和动作电位时程（APD）。动作电位和钙之间的相互作用，称为兴奋-收缩耦合，产生了丰富的非线性动力学谱，特别是在快速心率下，这对心脏收缩和致命性心律失常的发展非常重要。在这项研究中，我们开发了一个非线性迭代映射模型来研究周期性刺激细胞中心脏兴奋-收缩耦合的动力学。我们首先研究了由于APD恢复的非线性动力学，APD与其先前舒张间期之间的函数关系。然后，我们研究了由于细胞内钙循环的非线性动力学时，总细胞钙是恒定的或在节拍的基础上变化。最后，我们研究了两个动力学系统由于双向耦合而产生的非线性动力学。鞍结分叉导致双稳态，周期加倍分叉导致交替，和周期加倍路线混沌可以独立地发生在动作电位或细胞内钙循环子系统的心率增加。当两个动力系统耦合时，系统会发生Hopf分岔，导致系统的拟周期性.虽然这些动态预测从低维迭代地图，这里的方法提供了有价值的信息，可用作基础，探索生理详细的离子模型的动力学特征，照亮实验结果，并设计实验可测试的预测新的生物实验。
Cardiac myocytes are excitable cells in which an external current stimulus depolarizes the membrane potential to elicit an action potential. This action potential then triggers calcium release from intracellular stores, which mediates contraction. Conversely, intracellular calcium also modulates membrane currents, affecting action potential morphology and action potential duration (APD). The interactions between action potential and calcium, termed excitation-contraction coupling, give rise to a rich spectrum of nonlinear dynamics, especially at rapid heart rates, which are important for cardiac contraction and the development of lethal arrhythmias. In this study, we developed a nonlinear iterated map model to investigate the dynamics of cardiac excitation-contraction coupling in a periodically stimulated cell. We first studied the nonlinear dynamics due to APD restitution, a functional relation between APD and its preceding diastolic interval. We then studied the nonlinear dynamics due to intracellular calcium cycling when total cell calcium is constant or varies at a beat-to-beat basis. Finally, we studied the nonlinear dynamics due to the bidirectional coupling of the two dynamical systems. Saddle-node bifurcations leading to bistability, period-doubling bifurcations leading to alternans, and period-doubling routes to chaos can independently occur in both action potential or intracellular calcium cycling subsystems as heart rate increases. A Hopf bifurcation leading to quasiperiodicity occurs when the two dynamical systems are coupled. Although these dynamics are predicted from low-dimensional iterated maps, the approach here provides valuable information which can be used as a basis to explore dynamical features of physiologically detailed ionic models, to illuminate experimental findings, and to design experimentally testable predictions for new biological experiments.