Abstract We report a family of K + 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 + -selectivity filter. KCRs differ in that they are light-gated and they have independently evolved an alternative K + selectivity mechanism. The KCRs are potent, highly selective of K + over Na + , and open in less than 1 millisecond following photoactivation. Their permeability ratio P K /P Na 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 + 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. One-Sentence Summary Potassium-selective channelrhodopsins long-sought for optogenetic research and therapy of neurological and cardiac diseases.

Kalium rhodopsins: Natural light-gated potassium channels