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Calcium-permeable channelrhodopsins for the photocontrol of calcium signalling

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Item Type:Article
Title:Calcium-permeable channelrhodopsins for the photocontrol of calcium signalling
Creators: Fernandez Lahore, R.G. ORCID logoORCID: https://orcid.org/0000-0002-8559-2767, Pampaloni, N.P. ORCID logoORCID: https://orcid.org/0000-0002-4066-0295, Schiewer, E. ORCID logoORCID: https://orcid.org/0000-0001-7913-5597, Heim, M.M. ORCID logoORCID: https://orcid.org/0000-0002-8079-4204, Tillert, L. ORCID logoORCID: https://orcid.org/0000-0001-7497-018X, Vierock, J., Oppermann, J. ORCID logoORCID: https://orcid.org/0000-0002-3442-1458, Walther, J. ORCID logoORCID: https://orcid.org/0000-0001-6254-9128, Schmitz, D. ORCID logoORCID: https://orcid.org/0000-0003-2741-5241, Owald, D. ORCID logoORCID: https://orcid.org/0000-0001-7747-7884, Plested, A.J.R. ORCID logoORCID: https://orcid.org/0000-0001-6062-0832, Rost, B.R. ORCID logoORCID: https://orcid.org/0000-0003-1906-0081 and Hegemann, P. ORCID logoORCID: https://orcid.org/0000-0003-3589-6452
Abstract:Channelrhodopsins are light-gated ion channels used to control excitability of designated cells in large networks with high spatiotemporal resolution. While ChRs selective for H(+), Na(+), K(+) and anions have been discovered or engineered, Ca(+)-selective ChRs have not been reported to date. Here, we analyse ChRs and mutant derivatives with regard to their Ca(+) permeability and improve their Ca(+) affinity by targeted mutagenesis at the central selectivity filter. The engineered channels, termed CapChR1 and CapChR2 for calcium-permeable channelrhodopsins, exhibit reduced sodium and proton conductance in connection with strongly improved Ca(+) permeation at negative voltage and low extracellular Ca(+) concentrations. In cultured cells and neurons, CapChR2 reliably increases intracellular Ca(+) concentrations. Moreover, CapChR2 can robustly trigger Ca(+) signalling in hippocampal neurons. When expressed together with genetically encoded Ca(+) indicators in Drosophila melanogaster mushroom body output neurons, CapChRs mediate light-evoked Ca(+) entry in brain explants.
Keywords:Cellular Neuroscience, Optogenetics, Permeation and Transport, Animals, Drosophila Melanogaster
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group
Volume:13
Number:1
Page Range:7844
Date:21 December 2022
Additional Information:Erratum in : Nat Commun 15(1):3958.
Official Publication:https://doi.org/10.1038/s41467-022-35373-4
PubMed:View item in PubMed

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