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Diminishing neuronal acidification by channelrhodopsins with low proton conduction

Many channelrhodopsins are permeable to protons. We found that in neurons, activation of a high-current channelrhodopsin, CheRiff, led to significant acidification, with faster acidification in the dendrites than in the soma. Experiments with patterned optogenetic stimulation in monolayers of HEK ce...

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Autores principales: Hayward, Rebecca Frank, Brooks, F Phil, Yang, Shang, Gao, Shiqiang, Cohen, Adam E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10558203/
https://www.ncbi.nlm.nih.gov/pubmed/37801078
http://dx.doi.org/10.7554/eLife.86833
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author Hayward, Rebecca Frank
Brooks, F Phil
Yang, Shang
Gao, Shiqiang
Cohen, Adam E
author_facet Hayward, Rebecca Frank
Brooks, F Phil
Yang, Shang
Gao, Shiqiang
Cohen, Adam E
author_sort Hayward, Rebecca Frank
collection PubMed
description Many channelrhodopsins are permeable to protons. We found that in neurons, activation of a high-current channelrhodopsin, CheRiff, led to significant acidification, with faster acidification in the dendrites than in the soma. Experiments with patterned optogenetic stimulation in monolayers of HEK cells established that the acidification was due to proton transport through the opsin, rather than through other voltage-dependent channels. We identified and characterized two opsins which showed large photocurrents, but small proton permeability, PsCatCh2.0 and ChR2-3M. PsCatCh2.0 showed excellent response kinetics and was also spectrally compatible with simultaneous voltage imaging with QuasAr6a. Stimulation-evoked acidification is a possible source of disruptions to cell health in scientific and prospective therapeutic applications of optogenetics. Channelrhodopsins with low proton permeability are a promising strategy for avoiding these problems.
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spelling pubmed-105582032023-10-07 Diminishing neuronal acidification by channelrhodopsins with low proton conduction Hayward, Rebecca Frank Brooks, F Phil Yang, Shang Gao, Shiqiang Cohen, Adam E eLife Neuroscience Many channelrhodopsins are permeable to protons. We found that in neurons, activation of a high-current channelrhodopsin, CheRiff, led to significant acidification, with faster acidification in the dendrites than in the soma. Experiments with patterned optogenetic stimulation in monolayers of HEK cells established that the acidification was due to proton transport through the opsin, rather than through other voltage-dependent channels. We identified and characterized two opsins which showed large photocurrents, but small proton permeability, PsCatCh2.0 and ChR2-3M. PsCatCh2.0 showed excellent response kinetics and was also spectrally compatible with simultaneous voltage imaging with QuasAr6a. Stimulation-evoked acidification is a possible source of disruptions to cell health in scientific and prospective therapeutic applications of optogenetics. Channelrhodopsins with low proton permeability are a promising strategy for avoiding these problems. eLife Sciences Publications, Ltd 2023-10-06 /pmc/articles/PMC10558203/ /pubmed/37801078 http://dx.doi.org/10.7554/eLife.86833 Text en © 2023, Hayward et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Hayward, Rebecca Frank
Brooks, F Phil
Yang, Shang
Gao, Shiqiang
Cohen, Adam E
Diminishing neuronal acidification by channelrhodopsins with low proton conduction
title Diminishing neuronal acidification by channelrhodopsins with low proton conduction
title_full Diminishing neuronal acidification by channelrhodopsins with low proton conduction
title_fullStr Diminishing neuronal acidification by channelrhodopsins with low proton conduction
title_full_unstemmed Diminishing neuronal acidification by channelrhodopsins with low proton conduction
title_short Diminishing neuronal acidification by channelrhodopsins with low proton conduction
title_sort diminishing neuronal acidification by channelrhodopsins with low proton conduction
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10558203/
https://www.ncbi.nlm.nih.gov/pubmed/37801078
http://dx.doi.org/10.7554/eLife.86833
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