All-optical control of cardiac excitation: combined high-resolution optogenetic actuation and optical mapping.
All-optical control of cardiac excitation: combined high-resolution optogenetic actuation and optical mapping.
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DOI：
10.1113/jp271559
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发表时间：
2016-05-01
期刊：
影响因子：
--
通讯作者：
Bub G
中科院分区：
文献类型：
--
作者：
Entcheva E;Bub G
心脏组织是一个可兴奋的系统，可以支持复杂的时空动力学，包括致命后果的不稳定性（心律失常）。虽然在过去二十年中，兴奋（电压和钙动力学）的光学标测促进了这种心律失常事件的详细表征，但直到最近，还没有精确的工具来主动询问空间和时间上的心脏动力学。在这项工作中，我们讨论了空间和时间分辨的光遗传学驱动和心脏激发波的同时快速，高分辨率光学成像的新方法的组合使用。首先，概述了心肌细胞光诱导反应的机制、局限性和独特性。这些包括使用去极化和超极化视蛋白双向控制膜电位的能力;诱导长期持续电压变化的能力;以及控制心脏动作电位的不应性和形状的能力。在合胞体组织水平，我们讨论了光遗传学使细胞-细胞耦合，改变传导特性和终止传播波的光实验。特别注意使用动态光模式干扰正在进行的激活并探测所需组织位置处的电生理特性的光学刺激的空间和时间分辨应用。组合使用光学方法来扰动和观察系统可以提供用于心脏电活动的精确反馈控制的新工具，这在以前的药理学和电刺激中不可用。这些用于全光学电生理学的新实验工具允许精确操纵和量化心脏动力学，其鲁棒性与计算设置相当，并且可以为起搏，心律失常发生和抑制或心脏复律提供新的见解。
Cardiac tissue is an excitable system that can support complex spatiotemporal dynamics, including instabilities (arrhythmias) with lethal consequences. While over the last two decades optical mapping of excitation (voltage and calcium dynamics) has facilitated the detailed characterization of such arrhythmia events, until recently, no precise tools existed to actively interrogate cardiac dynamics in space and time. In this work, we discuss the combined use of new methods for space‐ and time‐resolved optogenetic actuation and simultaneous fast, high resolution optical imaging of cardiac excitation waves. First, the mechanisms, limitations and unique features of optically induced responses in cardiomyocytes are outlined. These include the ability to bidirectionally control the membrane potential using depolarizing and hyperpolarizing opsins; the ability to induce prolonged sustained voltage changes; and the ability to control refractoriness and the shape of the cardiac action potential. At the syncytial tissue level, we discuss optogenetically enabled experimentation on cell–cell coupling, alteration of conduction properties and termination of propagating waves by light. Specific attention is given to space‐ and time‐resolved application of optical stimulation using dynamic light patterns to perturb ongoing activation and to probe electrophysiological properties at desired tissue locations. The combined use of optical methods to perturb and to observe the system can offer new tools for precise feedback control of cardiac electrical activity, not available previously with pharmacological and electrical stimulation. These new experimental tools for all‐optical electrophysiology allow for a level of precise manipulation and quantification of cardiac dynamics comparable in robustness to the computational setting, and can provide new insights into pacemaking, arrhythmogenesis and suppression or cardioversion.