TY  - JOUR
AU  - Vierock, Johannes
AU  - Kaufmann, Joel C D
AU  - Faiß, Lukas
AU  - Tillert, Linda
AU  - Krause, Benjamin S
AU  - Fischer, Paul
AU  - Nguyen, Thi Bich Thao
AU  - Schmitz, Dietmar
AU  - Rost, Benjamin R
AU  - Bartl, Franz
AU  - Hegemann, Peter
TI  - Multicolor photoreactions of the red light-activated channelrhodopsin Chrimson.
JO  - Proceedings of the National Academy of Sciences of the United States of America
VL  - 122
IS  - 52
SN  - 0027-8424
CY  - Washington, DC
PB  - National Acad. of Sciences
M1  - DZNE-2025-01455
SP  - e2513375122
PY  - 2025
AB  - 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.
KW  - Channelrhodopsins: metabolism
KW  - Channelrhodopsins: chemistry
KW  - Channelrhodopsins: genetics
KW  - Light
KW  - Optogenetics: methods
KW  - Neurons: metabolism
KW  - Neurons: radiation effects
KW  - Humans
KW  - Animals
KW  - HEK293 Cells
KW  - Red Light
KW  - Chrimson (Other)
KW  - FTIR spectroscopy (Other)
KW  - channelrhodopsins (Other)
KW  - optogenetics (Other)
KW  - retinal prosthesis (Other)
KW  - Channelrhodopsins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41428877
DO  - DOI:10.1073/pnas.2513375122
UR  - https://pub.dzne.de/record/283048
ER  -