PT  - JOURNAL ARTICLE
AU  - Johannes Vierock
AU  - Enrico Peter
AU  - Christiane Grimm
AU  - Andrey Rozenberg
AU  - Alejandro G. Castro Scalise
AU  - Sandra Augustin
AU  - Dimitrii Tanese
AU  - Benoît C. Forget
AU  - Valentina Emiliani
AU  - Oded Béjà
AU  - Peter Hegemann
TI  - WiChR, a highly potassium selective channelrhodopsin for low-light two-photon neuronal inhibition
AID  - 10.1101/2022.07.02.498568
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.07.02.498568
4099  - http://biorxiv.org/content/early/2022/07/03/2022.07.02.498568.short
4100  - http://biorxiv.org/content/early/2022/07/03/2022.07.02.498568.full
AB  - 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 identify 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 an unmatched 80-fold preference for K+ over Na+, stable photocurrents under continuous illumination and a prolonged open state lifetime. Well expressed in neurons, WiChR allows two-photon inhibition at low irradiance and reduced tissue heating,_recommending WiChR as the long-awaited efficient and versatile optogenetic inhibitor.Competing Interest StatementThe authors have declared no competing interest.