WiChR, a highly potassium selective channelrhodopsin for low-light two-photon neuronal inhibition

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Vierock, Johannes | Peter, Enrico | Grimm, Christiane | Rozenberg, Andrey | Castro Scalise, Alejandro, G | Augustin, Sandra | Tanese, Dimitrii | Forget, Benoît, C | Emiliani, Valentina | Béjà, Oded | Hegemann, Peter

Edité par CCSD -

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.

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