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@ARTICLE{Vierock:283048,
      author       = {Vierock, Johannes and Kaufmann, Joel C D and Faiß, Lukas
                      and Tillert, Linda and Krause, Benjamin S and Fischer, Paul
                      and Nguyen, Thi Bich Thao and Schmitz, Dietmar and Rost,
                      Benjamin R and Bartl, Franz and Hegemann, Peter},
      title        = {{M}ulticolor photoreactions of the red light-activated
                      channelrhodopsin {C}hrimson.},
      journal      = {Proceedings of the National Academy of Sciences of the
                      United States of America},
      volume       = {122},
      number       = {52},
      issn         = {0027-8424},
      address      = {Washington, DC},
      publisher    = {National Acad. of Sciences},
      reportid     = {DZNE-2025-01455},
      pages        = {e2513375122},
      year         = {2025},
      abstract     = {Channelrhodopsins are light-gated ion channels that are
                      used in modern neurosciences for the precise control of
                      cellular ion fluxes by light. With a peak absorption at 585
                      nm, Chrimson is the most red-shifted cation-conducting ChR.
                      It is frequently employed in multicolor experiments
                      alongside blue light-sensitive optogenetic tools and is so
                      far the only light-gated ion channel successfully applied in
                      human vision restoration. However, its photoresponses to
                      different wavelengths have not been thoroughly
                      characterized. In this study, we identify multiple
                      interconvertible dark states of Chrimson with distinct
                      absorption and photokinetic properties. Combining
                      electrophysiology and spectroscopy with optogenetic
                      experiments in neurons, we unveil that this dark state
                      heterogeneity is based on distinct protonation dynamics of
                      the counterion complex and alternative retinal
                      isomerization. In neurons, prolonged red illumination
                      reduces Chrimson's red light sensitivity, which is reflected
                      by a blue shift of the action spectrum. Blue light pulses
                      reverse this shift and increase the excitability in
                      subsequent red-light flashes. This understanding of
                      wavelength-dependent photoreactions in Chrimson will improve
                      the design of multicolor optogenetic experiments and inform
                      strategies for optimizing Chrimson for therapeutic
                      applications.},
      keywords     = {Channelrhodopsins: metabolism / Channelrhodopsins:
                      chemistry / Channelrhodopsins: genetics / Light /
                      Optogenetics: methods / Neurons: metabolism / Neurons:
                      radiation effects / Humans / Animals / HEK293 Cells / Red
                      Light / Chrimson (Other) / FTIR spectroscopy (Other) /
                      channelrhodopsins (Other) / optogenetics (Other) / retinal
                      prosthesis (Other) / Channelrhodopsins (NLM Chemicals)},
      cin          = {AG Schmitz},
      ddc          = {500},
      cid          = {I:(DE-2719)1810004},
      pnm          = {351 - Brain Function (POF4-351)},
      pid          = {G:(DE-HGF)POF4-351},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41428877},
      doi          = {10.1073/pnas.2513375122},
      url          = {https://pub.dzne.de/record/283048},
}