最近，一項(xiàng)發(fā)表在《生物物理學(xué)雜志》上的研究稱,，人類心臟細(xì)胞跳動(dòng)的節(jié)律可以由光線控制。斯坦福大學(xué)的研究人員將藻類的一個(gè)基因插入了人類的胚胎干細(xì)胞,，之后又誘導(dǎo)胚胎干細(xì)胞分化成肌肉細(xì)胞,。基因表達(dá)一種光敏感通道蛋白(channelrhodopsin-2),，使得細(xì)胞通道可以在光的控制下自由關(guān)閉,。
這項(xiàng)技術(shù)未來可用于激活人類的竇房結(jié)細(xì)胞。“我們可以將這些光敏細(xì)胞注射進(jìn)入病人的心臟,，”論文的合作者Christopher Zarins說,，“這樣就可以實(shí)現(xiàn)對(duì)心臟的遠(yuǎn)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.
