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

Vierock, J.; Peter, E.; Grimm, C.; Rozenberg, A.; Castro Scalise, A. G.; Augustin, S.; Tanese, D.; Forget, B. C.; Emiliani, V.; Beja, O.; Hegemann, P.

doi:10.1101/2022.07.02.498568

bioRxiv · 10.1101/2022.07.02.498568

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

Vierock, J.·Peter, E.·Grimm, C.·Rozenberg, A.·Castro Scalise, A. G.·Augustin, S.·Tanese, D.·Forget, B. C.·Emiliani, V.·Beja, O.·Hegemann, P.

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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 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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Vierock, J., Peter, E., Grimm, C., Rozenberg, A., Castro Scalise, A. G., Augustin, S., Tanese, D., Forget, B. C., Emiliani, V., Beja, O., Hegemann, P.. 2022-07-03. WiChR, a highly potassium selective channelrhodopsin for low-light two-photon neuronal inhibition. https://doi.org/10.1101/2022.07.02.498568

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