Conversion of channelrhodopsin into a light-gated chloride channel

Standard

Conversion of channelrhodopsin into a light-gated chloride channel. / Wietek, Jonas; Wiegert, J Simon; Adeishvili, Nona; Schneider, Franziska; Watanabe, Hiroshi; Tsunoda, Satoshi P; Vogt, Arend; Elstner, Marcus; Oertner, Thomas G; Hegemann, Peter.

In: SCIENCE, Vol. 344, No. 6182, 25.04.2014, p. 409-12.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

Harvard

Wietek, J, Wiegert, JS, Adeishvili, N, Schneider, F, Watanabe, H, Tsunoda, SP, Vogt, A, Elstner, M, Oertner, TG & Hegemann, P 2014, 'Conversion of channelrhodopsin into a light-gated chloride channel', SCIENCE, vol. 344, no. 6182, pp. 409-12. https://doi.org/10.1126/science.1249375

APA

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), 409-12. https://doi.org/10.1126/science.1249375

Vancouver

Wietek J, Wiegert JS, Adeishvili N, Schneider F, Watanabe H, Tsunoda SP et al. Conversion of channelrhodopsin into a light-gated chloride channel. SCIENCE. 2014 Apr 25;344(6182):409-12. https://doi.org/10.1126/science.1249375

Bibtex

@article{0e5c82e1907341b3a42b92c6f3344b4d,
title = "Conversion of channelrhodopsin into a light-gated chloride channel",
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.",
keywords = "Action Potentials, Animals, Binding Sites, CA1 Region, Hippocampal, Chloride Channels, Chlorides, HEK293 Cells, Humans, Hydrogen Bonding, Ion Channel Gating, Light, Models, Molecular, Molecular Dynamics Simulation, Mutation, Patch-Clamp Techniques, Protein Conformation, Protein Engineering, Pyramidal Cells, Rats, Recombinant Fusion Proteins, Rhodopsin, Transfection",
author = "Jonas Wietek and Wiegert, {J Simon} and Nona Adeishvili and Franziska Schneider and Hiroshi Watanabe and Tsunoda, {Satoshi P} and Arend Vogt and Marcus Elstner and Oertner, {Thomas G} and Peter Hegemann",
year = "2014",
month = apr,
day = "25",
doi = "10.1126/science.1249375",
language = "English",
volume = "344",
pages = "409--12",
journal = "SCIENCE",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6182",

}

RIS

TY - JOUR

T1 - Conversion of channelrhodopsin into a light-gated chloride channel

AU - Wietek, Jonas

AU - Wiegert, J Simon

AU - Adeishvili, Nona

AU - Schneider, Franziska

AU - Watanabe, Hiroshi

AU - Tsunoda, Satoshi P

AU - Vogt, Arend

AU - Elstner, Marcus

AU - Oertner, Thomas G

AU - Hegemann, Peter

PY - 2014/4/25

Y1 - 2014/4/25

N2 - 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.

AB - 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.

KW - Action Potentials

KW - Animals

KW - Binding Sites

KW - CA1 Region, Hippocampal

KW - Chloride Channels

KW - Chlorides

KW - HEK293 Cells

KW - Humans

KW - Hydrogen Bonding

KW - Ion Channel Gating

KW - Light

KW - Models, Molecular

KW - Molecular Dynamics Simulation

KW - Mutation

KW - Patch-Clamp Techniques

KW - Protein Conformation

KW - Protein Engineering

KW - Pyramidal Cells

KW - Rats

KW - Recombinant Fusion Proteins

KW - Rhodopsin

KW - Transfection

U2 - 10.1126/science.1249375

DO - 10.1126/science.1249375

M3 - SCORING: Journal article

C2 - 24674867

VL - 344

SP - 409

EP - 412

JO - SCIENCE

JF - SCIENCE

SN - 0036-8075

IS - 6182

ER -