Cohen Ohad, Safran Samuel A
Department of Chemical and Biological Physics, Weizmann Institute of Science, Rehovot, Israel.
Front Physiol. 2020 Feb 28;11:164. doi: 10.3389/fphys.2020.00164. eCollection 2020.
We review a theoretical, coarse-grained description for cardiomyocytes calcium dynamics that is motivated by experiments on RyR channel dynamics and provides an analogy to other spontaneously oscillating systems. We show how a minimal model, that focuses on calcium channel and pump dynamics and kinetics, results in a single, easily understood equation for spontaneous calcium oscillations (the Van-der-Pol equation). We analyze experiments on isolated RyR channels to quantify how the channel dynamics depends both on the local calcium concentration, as well as its temporal behavior ("adaptation"). Our oscillator model analytically predicts the conditions for spontaneous oscillations, their frequency and amplitude, and how each of those scale with the small number of relevant parameters related to calcium channel and pump activity. The minimal model is easily extended to include the effects of noise and external pacing (electrical or mechanical). We show how our simple oscillator predicts and explains the experimental observations of synchronization, "bursting" and reduction of apparent noise in the beating dynamics of paced cells. Thus, our analogy and theoretical approach provides robust predictions for the beating dynamics, and their biochemical and mechanical modulation.
我们回顾了一种针对心肌细胞钙动力学的理论性、粗粒度描述，该描述受兰尼碱受体（RyR）通道动力学实验的启发，并为其他自发振荡系统提供了一种类比。我们展示了一个聚焦于钙通道和泵的动力学及动力学过程的最小模型，是如何得出一个用于自发钙振荡的简单易懂的单一方程（范德波尔方程）的。我们分析了分离的RyR通道实验，以量化通道动力学如何既依赖于局部钙浓度，又依赖于其时间行为（“适应性”）。我们的振荡器模型通过分析预测了自发振荡的条件、其频率和幅度，以及这些如何随与钙通道和泵活性相关的少量参数变化。这个最小模型很容易扩展以纳入噪声和外部起搏（电或机械）的影响。我们展示了我们的简单振荡器如何预测并解释在起搏细胞的搏动动力学中同步、“爆发”和表观噪声降低的实验观察结果。因此，我们的类比和理论方法为搏动动力学及其生化和机械调节提供了可靠的预测。
