Scientific article
OA Policy
English

WiChR, a highly potassium-selective channelrhodopsin for low-light one- and two-photon inhibition of excitable cells

Published inScience advances, vol. 8, no. 49, eadd7729
Publication date2022-12-09
First online date2022-12-09
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.

Keywords
  • Channelrhodopsins / genetics
  • Channelrhodopsins / metabolism
  • Light
  • Neurons / physiology
  • Optogenetics
  • Potassium / metabolism
  • Sodium / metabolism
Affiliation entities Not a UNIGE publication
Funding
  • European Commission - Personalized Therapies for Atrial Fibrillation. A Translational Approach [860974]
Citation (ISO format)
VIEROCK, Johannes et al. WiChR, a highly potassium-selective channelrhodopsin for low-light one- and two-photon inhibition of excitable cells. In: Science advances, 2022, vol. 8, n° 49, p. eadd7729. doi: 10.1126/sciadv.add7729
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Article (Published version)
Identifiers
Additional URL for this publicationhttps://www.science.org/doi/10.1126/sciadv.add7729
Journal ISSN2375-2548
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