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Kalium channelrhodopsins are natural light-gated potassium channels that mediate optogenetic inhibition
Nature Neuroscience ( IF 21.2 ) Pub Date : 2022-06-20 , DOI: 10.1038/s41593-022-01094-6
Elena G Govorunova 1 , Yueyang Gou 2, 3 , Oleg A Sineshchekov 1 , Hai Li 1 , Xiaoyu Lu 4 , Yumei Wang 1 , Leonid S Brown 5 , François St-Pierre 2, 4, 6, 7 , Mingshan Xue 2, 3, 8 , John L Spudich 1
Affiliation  

Channelrhodopsins are used widely for optical control of neurons, in which they generate photoinduced proton, sodium or chloride influx. Potassium (K+) is central to neuron electrophysiology, yet no natural K+-selective light-gated channel has been identified. Here, we report kalium channelrhodopsins (KCRs) from Hyphochytrium catenoides. Previously known gated potassium channels are mainly ligand- or voltage-gated and share a conserved K+-selectivity filter. KCRs differ in that they are light-gated and have independently evolved an alternative K+ selectivity mechanism. The KCRs are potent, highly selective of K+ over Na+, and open in less than 1 ms following photoactivation. The permeability ratio PK/PNa of 23 makes H. catenoides KCR1 (HcKCR1) a powerful hyperpolarizing tool to suppress excitable cell firing upon illumination, demonstrated here in mouse cortical neurons. HcKCR1 enables optogenetic control of K+ gradients, which is promising for the study and potential treatment of potassium channelopathies such as epilepsy, Parkinson’s disease and long-QT syndrome and other cardiac arrhythmias.



中文翻译:

钾通道视紫红质是介导光遗传学抑制的天然光门控钾通道

视紫红质通道广泛用于神经元的光学控制,其中它们产生光诱导的质子、钠或氯离子流入。钾 (K + ) 是神经元电生理学的核心,但尚未发现天然的 K +选择性光门控通道。在这里,我们报道了来自丝状菌的钾通道视紫红质(KCR) 。先前已知的门控钾通道主要是配体门控或电压门控的,并且共享保守的K +选择性过滤器。KCR 的不同之处在于它们是光门控的,并独立进化出另一种 K +选择性机制。KCR 是有效的,对 K +的选择性高于 Na +,并且在光激活后不到 1 毫秒内打开。通透性比率P K / P Na为 23,使H. catenoides KCR1 ( Hc KCR1) 成为一种强大的超极化工具,可抑制光照时的兴奋性细胞放电,这一点在小鼠皮质神经元中得到了证明。Hc KCR1 能够实现 K +梯度的光遗传学控制,这对于癫痫、帕金森病、长 QT 综合征和其他心律失常等钾离子通道病的研究和潜在治疗具有广阔的前景。

更新日期:2022-06-20
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