WiChR, a highly potassium-selective channelrhodopsin for low-light one- and two-photon inhibition of excitable cells
Johannes Vierock, Enrico Peter, Christiane Grimm, Andrey Rozenberg, I-Wen Chen, Linda Tillert, Alejandro G. Castro Scalise, M.L. Casini, Sandra Augustin, Dimitrii Tanese, Benoı̂t C. Forget, Rémi Peyronnet, Franziska Schneider‐Warme, Valentina Emiliani, Oded Béjà, Peter Hegemann
Abstract
The electric excitability of muscle, heart, and brain tissue relies on the precise interplay of Na + - and K + -selective ion channels. The involved ion fluxes are controlled in optogenetic studies using light-gated channelrhodopsins (ChRs). While non-selective cation-conducting ChRs are well established for excitation, K + -selective ChRs (KCRs) for efficient inhibition have only recently come into reach. Here, we report the molecular analysis of recently discovered KCRs from the stramenopile Hyphochytrium catenoides and identification of a novel type of hydrophobic K + selectivity filter. Next, we demonstrate that the KCR signature motif is conserved in related stramenopile ChRs. Among them, WiChR from Wobblia lunata features a so far unmatched preference for K + over Na + , stable photocurrents under continuous illumination, and a prolonged open-state lifetime. Showing high expression levels in cardiac myocytes and neurons, WiChR allows single- and two-photon inhibition at low irradiance and reduced tissue heating. Therefore, we recommend WiChR as the long-awaited efficient and versatile optogenetic inhibitor.