A comprehensive multiscale framework for simulating optogenetics in the heart
A comprehensive multiscale framework for simulating optogenetics in the heart
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DOI：
10.1038/ncomms3370
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发表时间：
2013-08-01
影响因子：
16.6
通讯作者：
Trayanova, Natalia A.
中科院分区：
文献类型：
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作者：
Boyle, Patrick M.;Williams, John C.;Trayanova, Natalia A.
光遗传学已成为心脏电控制的替代方法，其中照明用于在经修饰以表达光敏蛋白（视蛋白）的组织中引发生物电响应。该技术有望在靶细胞或组织中唤起时空精确的反应，从而为改善心脏功能的安全有效的治疗方法创造新的可能性。在这里，我们提出了一个全面的框架，心脏光遗传学的多尺度建模，允许机械检查的光学控制和潜在的治疗应用的探索。该框架结合了视蛋白通道动力学和传递模式，光敏细胞的空间分布和组织照明约束的准确表示，使得有可能在子器官尺度的相互作用所产生的紧急行为的预测。我们应用这个框架来探索光遗传学传递特性如何决定光刺激的能量要求，并确定具有低光激发阈值的潜在起搏靶点的心脏结构。
Optogenetics has emerged as an alternative method for electrical control of the heart, where illumination is used to elicit a bioelectric response in tissue modified to express photosensitive proteins (opsins). This technology promises to enable evocation of spatiotemporally precise responses in targeted cells or tissues, thus creating new possibilities for safe and effective therapeutic approaches to ameliorate cardiac function. Here we present a comprehensive framework for multiscale modelling of cardiac optogenetics, allowing both mechanistic examination of optical control and exploration of potential therapeutic applications. The framework incorporates accurate representations of opsin channel kinetics and delivery modes, spatial distribution of photosensitive cells, and tissue illumination constraints, making possible the prediction of emergent behaviour resulting from interactions at sub-organ scales. We apply this framework to explore how optogenetic delivery characteristics determine energy requirements for optical stimulation and to identify cardiac structures that are potential pacemaking targets with low optical excitation thresholds.