Cl-out is a novel cooperative optogenetic tool for extruding chloride from neurons.
Cl-out is a novel cooperative optogenetic tool for extruding chloride from neurons.
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DOI：
10.1038/ncomms13495
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发表时间：
2016-11-17
影响因子：
16.6
通讯作者：
Trevelyan, Andrew J.
中科院分区：
文献类型：
--
作者：
Alfonsa, Hannah;Lakey, Jeremy H.;Lightowlers, Robert N.;Trevelyan, Andrew J.
氯化物调节以多种方式影响大脑功能，例如，通过决定gaba能逆转电位，从而影响神经元的兴奋性和峰值时间。与此一致的是，越来越多的证据表明氯化物与一系列神经系统疾病有关。然而，由于控制氯化物水平的工具范围有限，对这些条件的调查变得困难。特别是，没有办法主动地从神经元中去除氯；我们现在描述一种光遗传学策略，“Cl-out”，来做到这一点。Cl-out通过质子泵、古紫红质和氯离子通道视蛋白这两种不同的视蛋白组分的协同作用来实现其作用。当两者同时被激活时，氯离子的去除就发生了，使用古紫质作为光学电压钳，通过同时打开的氯离子通道为氯离子的去除提供驱动力。我们进一步表明，这种新的光遗传策略可以逆转体外癫痫表型。氯化物调节对于设定gaba能逆转电位很重要，尽管控制氯化物水平的工具有限。在这里，作者将古紫红质与氯通道视蛋白结合在一起，产生光遗传氯挤出策略，“Cl-out”，他们在海马体切片中证明了这一点。
Chloride regulation affects brain function in many ways, for instance, by dictating the GABAergic reversal potential, and thereby influencing neuronal excitability and spike timing. Consistent with this, there is increasing evidence implicating chloride in a range of neurological conditions. Investigations about these conditions, though, are made difficult by the limited range of tools available to manipulate chloride levels. In particular, there has been no way to actively remove chloride from neurons; we now describe an optogenetic strategy, ‘Cl-out', to do exactly this. Cl-out achieves its effect by the cooperative action of two different component opsins: the proton pump, Archaerhodopsin and a chloride channel opsin. The removal of chloride happens when both are activated together, using Archaerhodopsin as an optical voltage clamp to provide the driving force for chloride removal through the concurrently opened, chloride channels. We further show that this novel optogenetic strategy can reverse an in vitro epileptogenic phenotype. Chloride regulation is important for setting GABAergic reversal potential, though tools to manipulate chloride levels are limited. Here, the authors combine Archaerhodopsin with a chloride channel opsin to generate an optogenetic chloride extrusion strategy, ‘Cl-out', which they demonstrate in hippocampal slices.
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影响因子：
64.8
作者：
COBB, SR;BUHL, EH;SOMOGYI, P
通讯作者：
SOMOGYI, P
影响因子：
5.3
作者：
Alfonsa, Hannah;Merricks, Edward M.;Trevelyan, Andrew J.
通讯作者：
Trevelyan, Andrew J.
影响因子：
2.5
作者：
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影响因子：
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作者：
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通讯作者：
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作者：
Deisseroth, Karl
通讯作者：
Deisseroth, Karl