Conversion of channelrhodopsin into a light-gated chloride channel

Jonas Wietek, J. Simon Wiegert, Nona Adeishvili, Franziska Schneider, Hiroshi Watanabe, Satoshi P. Tsunoda, Arend Vogt, Marcus Elstner, Thomas G. Oertner, Peter Hegemann

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208 Citations (Scopus)

Abstract

The field of optogenetics uses channelrhodopsins (ChRs) for light-induced neuronal activation. However, optimized tools for cellular inhibition at moderate light levels are lacking. We found that replacement of E90 in the central gate of ChR with positively charged residues produces chloride-conducting ChRs (ChloCs) with only negligible cation conductance. Molecular dynamics modeling unveiled that a high-affinity Cl--binding site had been generated near the gate. Stabilizing the open state dramatically increased the operational light sensitivity of expressing cells (slow ChloC). In CA1 pyramidal cells, ChloCs completely inhibited action potentials triggered by depolarizing current injections or synaptic stimulation. Thus, by inverting the charge of the selectivity filter, we have created a class of directly light-gated anion channels that can be used to block neuronal output in a fully reversible fashion.

Original languageEnglish
Pages (from-to)409-412
Number of pages4
JournalScience
Volume344
Issue number6182
DOIs
Publication statusPublished - 2014 Jan 1
Externally publishedYes

ASJC Scopus subject areas

  • General

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    Wietek, J., Wiegert, J. S., Adeishvili, N., Schneider, F., Watanabe, H., Tsunoda, S. P., Vogt, A., Elstner, M., Oertner, T. G., & Hegemann, P. (2014). Conversion of channelrhodopsin into a light-gated chloride channel. Science, 344(6182), 409-412. https://doi.org/10.1126/science.1249375