Diminishing neuronal acidification by channelrhodopsins with low proton conduction.
Journal
bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187
Informations de publication
Date de publication:
14 Sep 2023
14 Sep 2023
Historique:
pubmed:
18
2
2023
medline:
18
2
2023
entrez:
17
2
2023
Statut:
epublish
Résumé
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. Acidification is an undesirable artifact of optogenetic stimulation. Low proton-permeability opsins minimize this artifact while still allowing robust optogenetic control.
Identifiants
pubmed: 36798192
doi: 10.1101/2023.02.07.527404
pmc: PMC9934520
pii:
doi:
Types de publication
Preprint
Langues
eng
Commentaires et corrections
Type : UpdateIn
Références
Nat Biomed Eng. 2023 Apr;7(4):349-369
pubmed: 35027688
J Neurosci. 2011 May 18;31(20):7300-11
pubmed: 21593314
Neurochem Int. 2003 Jul;43(1):9-17
pubmed: 12605878
Nature. 2020 Aug;584(7819):98-101
pubmed: 32581357
Biomed Opt Express. 2017 Nov 29;8(12):5794-5813
pubmed: 29296505
Nature. 2019 May;569(7756):413-417
pubmed: 31043747
Elife. 2019 Jan 14;8:
pubmed: 30638447
Biochemistry. 1979 May 29;18(11):2210-8
pubmed: 36128
Neuron. 2014 Jan 22;81(2):314-20
pubmed: 24462096
Physiol Rev. 1989 Apr;69(2):315-82
pubmed: 2538851
Front Cell Neurosci. 2022 Jan 24;15:800313
pubmed: 35140589
Brain Stimul. 2020 May - Jun;13(3):881-890
pubmed: 32289721
Cell Res. 2017 Sep;27(9):1083-1099
pubmed: 28675158
J Neurosci. 2011 May 11;31(19):6997-7004
pubmed: 21562261
J Cell Biol. 2014 Nov 10;207(3):419-32
pubmed: 25385186
J Neurophysiol. 2009 Sep;102(3):1984-93
pubmed: 19625534
Physiol Rev. 1997 Jan;77(1):51-74
pubmed: 9016300
Trends Neurosci. 1992 Oct;15(10):396-402
pubmed: 1279865
Proc Natl Acad Sci U S A. 2016 Jan 12;113(2):E229-38
pubmed: 26627720
Sci Transl Med. 2013 Mar 20;5(177):177ps5
pubmed: 23515075
Brain Res. 2000 Oct 20;881(1):77-87
pubmed: 11033097
J Neurosci. 2019 Jun 19;39(25):4889-4908
pubmed: 30952812
FEBS Lett. 2013 Jun 27;587(13):1923-8
pubmed: 23669358
Nat Neurosci. 2009 Feb;12(2):229-34
pubmed: 19079251
Nature. 1998 Jul 9;394(6689):192-5
pubmed: 9671304
Elife. 2017 Aug 08;6:
pubmed: 28784204
Nat Med. 2021 Jul;27(7):1223-1229
pubmed: 34031601
Sci Rep. 2017 Aug 30;7(1):9928
pubmed: 28855540
Physiol Rev. 2003 Oct;83(4):1183-221
pubmed: 14506304
Elife. 2016 May 24;5:
pubmed: 27215841
Biophys Rev. 2020 Apr;12(2):453-459
pubmed: 32166612
J Am Chem Soc. 2015 Aug 26;137(33):10767-76
pubmed: 26237573
Gene Ther. 2012 Feb;19(2):169-75
pubmed: 21993174
J Biol Chem. 2013 Oct 11;288(41):29911-22
pubmed: 23995841
Proc Natl Acad Sci U S A. 2013 Nov 12;110(46):E4362-8
pubmed: 24163350
Nat Commun. 2013;4:1376
pubmed: 23340416
J Am Chem Soc. 2022 Mar 9;144(9):3771-3775
pubmed: 35175032
Brain Res. 1996 Jan 15;706(2):210-6
pubmed: 8822358
Cell Rep. 2022 May 24;39(8):110850
pubmed: 35613578
J Am Chem Soc. 2014 Feb 12;136(6):2529-37
pubmed: 24428326
Signal Transduct Target Ther. 2022 Apr 18;7(1):104
pubmed: 35430811
Nat Methods. 2014 Aug;11(8):825-33
pubmed: 24952910