Kalium channelrhodopsins are natural light-gated potassium channels that mediate optogenetic inhibition.
Kalium channelrhodopsins are natural light-gated potassium channels that mediate optogenetic inhibition.
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钾通道视紫红质是一种天然的光门控钾通道，介导光遗传抑制。
DOI：
10.1038/s41593-022-01094-6
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发表时间：
2022-07
影响因子：
25
通讯作者：
Spudich, John L.
中科院分区：
文献类型：
--
作者：
Govorunova, Elena G.;Gou, Yueyang;Sineshchekov, Oleg A.;Li, Hai;Lu, Xiaoyu;Wang, Yumei;Brown, Leonid S.;St-Pierre, Francois;Xue, Mingshan;Spudich, John L.
视紫红质广泛用于神经元的光学控制，其中它们产生光诱导的质子、钠或氯内流。钾（K+）是神经元电生理学的中心，但还没有天然的K+选择性光门控通道已被确定。在这里，我们报告钾通道视紫红质（KCRs）从Hyphochytrium catenoides。以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，并且已经独立地进化出替代的K+选择性机制。KCR是有效的，对K+的选择性高于Na+，并且在光活化后不到1 ms内打开。渗透性比值PK/PNa = 23时，H. catenoides KCR 1（HcKCR 1）是一种强大的超极化工具，可以抑制照明时的兴奋细胞放电，在小鼠皮层神经元中得到证实。HcKCR 1能够实现K+梯度的光遗传学控制，这对于钾通道病如癫痫、帕金森病和长QT综合征以及其他心律失常的研究和潜在治疗是有希望的。
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.
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影响因子：
14.9
作者：
Letunic I;Bork P
通讯作者：
Bork P
影响因子：
64.5
作者：
Kishi KE;Kim YS;Fukuda M;Inoue M;Kusakizako T;Wang PY;Ramakrishnan C;Byrne EFX;Thadhani E;Paggi JM;Matsui TE;Yamashita K;Nagata T;Konno M;Quirin S;Lo M;Benster T;Uemura T;Liu K;Shibata M;Nomura N;Iwata S;Nureki O;Dror RO;Inoue K;Deisseroth K;Kato HE
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25
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Adesnik, Hillel;Abdeladim, Lamiae
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Abdeladim, Lamiae
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62.1
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Ernst, Oliver P.;Lodowski, David T.;Elstner, Marcus;Hegemann, Peter;Brown, Leonid S.;Kandori, Hideki
通讯作者：
Kandori, Hideki
影响因子：
25
作者：
Mahn M;Prigge M;Ron S;Levy R;Yizhar O
通讯作者：
Yizhar O