Optogenetic Control of Cardiac Function

Optogenetic Control of Cardiac Function
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DOI:
10.1126/science.1195929
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发表时间:
2010-11-12
期刊:
影响因子:
56.9
通讯作者:
Huisken, Jan
Huisken, Jan
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Arrenberg, Aristides B.;Stainier, Didier Y. R.;Huisken, Jan

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心脏起搏器控制心脏收缩的节律性,作为最后的手段,可以被电池供电的设备取代。我们通过在斑马鱼心肌细胞中表达卤视紫质和通道视紫红质,创造了一种基因编码的、光学控制的起搏器。使用选择性平面照明显微镜中的图案照明,我们定位了起搏器,并模拟了心动过速、心动过缓、房室传导阻滞和心脏骤停。起搏器在发育过程中汇聚到窦房区,在心脏循环时由不到12个细胞组成。这些细胞活动的扰动是完全可逆的,表明了内源性起搏器的弹性。我们的研究结合了光遗传学和光片显微镜来揭示发育过程中器官功能的出现。
The cardiac pacemaker controls the rhythmicity of heart contractions and can be substituted by a battery-operated device as a last resort. We created a genetically encoded, optically controlled pacemaker by expressing halorhodopsin and channelrhodopsin in zebrafish cardiomyocytes. Using patterned illumination in a selective plane illumination microscope, we located the pacemaker and simulated tachycardia, bradycardia, atrioventricular blocks, and cardiac arrest. The pacemaker converges to the sinoatrial region during development and comprises fewer than a dozen cells by the time the heart loops. Perturbation of the activity of these cells was entirely reversible, demonstrating the resilience of the endogenous pacemaker. Our studies combine optogenetics and light-sheet microscopy to reveal the emergence of organ function during development.