最近，一项发表在《生物物理学杂志》上的研究称，人类心脏细胞跳动的节律可以由光线控制。斯坦福大学的研究人员将藻类的一个基因插入了人类的胚胎干细胞，之后又诱导胚胎干细胞分化成肌肉细胞。基因表达一种光敏感通道蛋白(channelrhodopsin-2)，使得细胞通道可以在光的控制下自由关闭。
这项技术未来可用于激活人类的窦房结细胞。“我们可以将这些光敏细胞注射进入病人的心脏，”论文的合作者Christopher Zarins说，“这样就可以实现对心脏的远程光控。”(生物谷 Bioon.com)
doi:10.1016/j.bpj.2011.08.004
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Multiscale Computational Models for Optogenetic Control of Cardiac Function
Oscar J. Abilez, , Jonathan Wong, Rohit Prakash, , Karl Deisseroth, , Christopher K. Zarins and Ellen Kuhl
The ability to stimulate mammalian cells with light has significantly changed our understanding of electrically excitable tissues in health and disease, paving the way toward various novel therapeutic applications. Here, we demonstrate the potential of optogenetic control in cardiac cells using a hybrid experimental/computational technique. Experimentally, we introduced channelrhodopsin-2 into undifferentiated human embryonic stem cells via a lentiviral vector, and sorted and expanded the genetically engineered cells. Via directed differentiation, we created channelrhodopsin-expressing cardiomyocytes, which we subjected to optical stimulation. To quantify the impact of photostimulation, we assessed electrical, biochemical, and mechanical signals using patch-clamping, multielectrode array recordings, and video microscopy. Computationally, we introduced channelrhodopsin-2 into a classic autorhythmic cardiac cell model via an additional photocurrent governed by a light-sensitive gating variable. Upon optical stimulation, the channel opens and allows sodium ions to enter the cell, inducing a fast upstroke of the transmembrane potential. We calibrated the channelrhodopsin-expressing cell model using single action potential readings for different photostimulation amplitudes, pulse widths, and frequencies. To illustrate the potential of the proposed approach, we virtually injected channelrhodopsin-expressing cells into different locations of a human heart, and explored its activation sequences upon optical stimulation. Our experimentally calibrated computational toolbox allows us to virtually probe landscapes of process parameters, and identify optimal photostimulation sequences toward pacing hearts with light.
