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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 Name:Fernandez Lahore, R.G., Pampaloni, N.P., Schiewer, E., Heim, M.M., Tillert, L., Vierock, J., Oppermann, J., Walther, J., Schmitz, D., Owald, D., Plested, A.J.R., Rost, B.R. and Hegemann, P.
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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