小柯机器人

科学家发现新型光门控钾离子通道
2022-06-22 16:55

2022年6月20日出版的《自然-神经科学》杂志发表了美国德克萨斯大学John L. Spudich课题组的最新成果,他们研究发现钾离子(K+)通道视紫红质是一种天然的光门控钾通道,介导光发生抑制。

研究人员揭示了Hyphochytrium catenoides的钾离子通道视紫红质(KCRs)。之前已知的门控钾离子通道主要是配体门控或电压门控,并共享一个保守的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+的选择性高于对Na+的选择性,并且在光活化后不到1 ms的时间内打开。

23的通透性比率PK/PNa 使H. catenoides KCR1(HcKCR1)成为一种强大的超极化工具,可抑制光照时可兴奋细胞放电,这在小鼠皮层神经元中得到了证明。HcKCR1可实现K+梯度的光遗传学控制,这对于钾离子通道引起的疾病(如癫痫、帕金森病和长QT综合征和其他心律失常)的研究和潜在治疗具有参考价值。

据了解,通道视紫红质广泛用于神经元的光学控制,它们产生光诱导性质子、钠或氯化物流入。钾离子是神经元电生理学的核心,但尚未发现天然K+选择性光门控通道。

附:英文原文

Title: Kalium channelrhodopsins are natural light-gated potassium channels that mediate optogenetic inhibition

Author: Govorunova, Elena G., Gou, Yueyang, Sineshchekov, Oleg A., Li, Hai, Lu, Xiaoyu, Wang, Yumei, Brown, Leonid S., St-Pierre, Franois, Xue, Mingshan, Spudich, John L.

Issue&Volume: 2022-06-20

Abstract: 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 1ms 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.

DOI: 10.1038/s41593-022-01094-6

Source: https://www.nature.com/articles/s41593-022-01094-6

Nature Neuroscience:《自然—神经科学》,创刊于1998年。隶属于施普林格·自然出版集团,最新IF:28.771
官方网址:https://www.nature.com/neuro/
投稿链接:https://mts-nn.nature.com/cgi-bin/main.plex


本期文章:《自然—神经科学》:Online/在线发表

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