Abstract

<h3>Abstract</h3> We report a family of K<sup>+</sup> channels, kalium channelrhodopsins (KCRs) from a fungus-like protist. Previously known potassium channels, widespread and mainly ligand- or voltage-gated, share a conserved pore-forming domain and K<sup>+</sup>-selectivity filter. KCRs differ in that they are light-gated and they have independently evolved an alternative K<sup>+</sup> selectivity mechanism. The KCRs are potent, highly selective of K<sup>+</sup> over Na<sup>+</sup>, and open in less than 1 millisecond following photoactivation. Their permeability ratio P<sub>K</sub>/P<sub>Na</sub> of ∼ 20 make KCRs powerful hyperpolarizing tools that suppress excitable cell firing upon illumination, demonstrated here in mouse cortical neurons. KCRs enable specific optogenetic photocontrol of K<sup>+</sup> gradients promising for the study and potential treatment of potassium channelopathies such as epilepsy, Parkinson’s disease, and long-QT syndrome and other cardiac arrhythmias. <h3>One-Sentence Summary</h3> Potassium-selective channelrhodopsins long-sought for optogenetic research and therapy of neurological and cardiac diseases.

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