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

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 P K /P Na 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.