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A red-light gate for a cation channel: The conducting state of channelrhodopsin-1 from Chlamydomonas augustae.

Overview

Authors: Istvan Szundi1, Vera Muders2, Chie Funatogawa1, David S. Kliger1, Ramona Schlesinger2, Joachim Heberle3
ORCID iDs: Istvan Szundi, Vera Muders, Chie Funatogawa, David S. Kliger, Ramona Schlesinger, Joachim Heberle
  1. Department of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, California
  2. Freie Universität Berlin, Department of Physics, Genetic Biophysics, Berlin, Germany
  3. Freie Universität Berlin, Department of Physics, Experimental Molecular Biophysics, Berlin, Germany
Institutions: University of California, Santa Cruz (United States); Freie Universität Berlin (Germany)
Journal: Biophysical journal, volume 125, issue 10, pages 2432-2447
Dates: received 4 December 2025; accepted 6 March 2026; published online 10 March 2026; in print 19 May 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.bpj.2026.03.019 · PMID 41808401 · PMCID PMC13351985 · OpenAlex W7134845633
Open access: hybrid, a free copy (OpenAlex)
Status: code on request
Categories: cellular / molecular (subfield)
Methods: Graphs
MeSH: Channelrhodopsins*, Chlamydomonas*, Electric Conductivity*, Ion Channel Gating*, Kinetics, Red Light (* major topic)
Topic: Photoreceptor and optogenetics research (Cellular and Molecular Neuroscience, Neuroscience), according to OpenAlex
Funding: Deutsche Forschungsgemeinschaft (DFG); UniSysCat (390540038); NIH (R01 EY029343)
Citations: cited by 1 paper (Europe PMC); 45 references in the paper

Abstract

Channelrhodopsins (ChRs) are light-controlled ion channels that have become indispensable tools in the field of optogenetics. Channelrhodopsin-1 from Chlamydomonas augustae (CaChR1) is a phylogenetically early member of this class of proteins with red-shifted absorption and pronounced photocurrent kinetics, but the exact correlation between its photocycle intermediate states and channel conductivity remains to be elucidated. Here, we use time-resolved optical absorption spectroscopy (TROD) in the nanosecond-to-second range for wild-type (WT) CaChR1 and its E169Q and D299N counterion variants. Singular value decomposition and global exponential fitting revealed kinetic complexity, suggesting parallel photocycle pathways and isospectral intermediates. The spectral deconvolution method resolved five fundamental spectral forms (K, L, M, N, and R) present in the kinetics. Analysis of their temporal evolution, combined with published electrophysiological data, allowed us to identify the conductive state. Contrary to the dominant model that associates conductivity with the deprotonated M state, we show that a late, red-shifted intermediate state, spectrally similar to the K state and called the O state, is the conductive state. The time evolution of this O state parallels that of the channel current in the WT and is consistent with the reduced conduction in the E169Q and D299N variants. Our findings establish a unified mechanism for channel gating in microbial rhodopsins, where a red-shifted intermediate state controls conduction, and provide a new framework for the rational design of optogenetic tools.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Versions

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Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 6 authors, 6 MeSH terms, 3 funders, 45 references.

Cite

This paper

Szundi, I., Muders, V., Funatogawa, C., Kliger, D. S., Schlesinger, R., & Heberle, J. (2026). A red-light gate for a cation channel: The conducting state of channelrhodopsin-1 from Chlamydomonas augustae. Biophysical journal, 125(10), 2432-2447. https://doi.org/10.1016/j.bpj.2026.03.019

BibTeX

@article{szundi2026red,
author = {Szundi, Istvan and Muders, Vera and Funatogawa, Chie and Kliger, David S. and Schlesinger, Ramona and Heberle, Joachim},
title = {{A red-light gate for a cation channel: The conducting state of channelrhodopsin-1 from Chlamydomonas augustae}},
journal = {Biophysical journal},
year = {2026},
month = mar,
volume = {125},
number = {10},
pages = {2432--2447},
publisher = {The Biophysical Society},
issn = {0006-3495},
doi = {10.1016/j.bpj.2026.03.019},
url = {https://doi.org/10.1016/j.bpj.2026.03.019},
pmid = {41808401},
pmcid = {PMC13351985}
}

RIS

TY - JOUR
AU - Szundi, Istvan
AU - Muders, Vera
AU - Funatogawa, Chie
AU - Kliger, David S.
AU - Schlesinger, Ramona
AU - Heberle, Joachim
TI - A red-light gate for a cation channel: The conducting state of channelrhodopsin-1 from Chlamydomonas augustae
T2 - Biophysical journal
J2 - Biophys J
PY - 2026
DA - 2026/03/10
VL - 125
IS - 10
SP - 2432
EP - 2447
SN - 0006-3495
PB - The Biophysical Society
DO - 10.1016/j.bpj.2026.03.019
UR - https://doi.org/10.1016/j.bpj.2026.03.019
LA - en
ER -

CSL-JSON

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