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Calcium-permeable channelrhodopsins for the photocontrol of calcium signalling

Author

Listed:
  • Rodrigo G. Fernandez Lahore

    (Humboldt-Universität zu Berlin)

  • Niccolò P. Pampaloni

    (Leibniz-Institut für Molekulare Pharmakologie
    Humboldt-Universität zu Berlin)

  • Enrico Schiewer

    (Humboldt-Universität zu Berlin)

  • M.-Marcel Heim

    (Charité – Universitätsmedizin Berlin)

  • Linda Tillert

    (Humboldt-Universität zu Berlin
    Charité – Universitätsmedizin Berlin)

  • Johannes Vierock

    (Humboldt-Universität zu Berlin
    Charité – Universitätsmedizin Berlin)

  • Johannes Oppermann

    (Humboldt-Universität zu Berlin)

  • Jakob Walther

    (Charité – Universitätsmedizin Berlin)

  • Dietmar Schmitz

    (Charité – Universitätsmedizin Berlin
    German Center for Neurodegenerative Diseases (DZNE))

  • David Owald

    (Charité – Universitätsmedizin Berlin)

  • Andrew J. R. Plested

    (Leibniz-Institut für Molekulare Pharmakologie
    Humboldt-Universität zu Berlin)

  • Benjamin R. Rost

    (German Center for Neurodegenerative Diseases (DZNE))

  • Peter Hegemann

    (Humboldt-Universität zu Berlin)

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, Ca2+-selective ChRs have not been reported to date. Here, we analyse ChRs and mutant derivatives with regard to their Ca2+ permeability and improve their Ca2+ 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 Ca2+ permeation at negative voltage and low extracellular Ca2+ concentrations. In cultured cells and neurons, CapChR2 reliably increases intracellular Ca2+ concentrations. Moreover, CapChR2 can robustly trigger Ca2+ signalling in hippocampal neurons. When expressed together with genetically encoded Ca2+ indicators in Drosophila melanogaster mushroom body output neurons, CapChRs mediate light-evoked Ca2+ entry in brain explants.

Suggested Citation

  • Rodrigo G. Fernandez Lahore & Niccolò P. Pampaloni & Enrico Schiewer & M.-Marcel Heim & Linda Tillert & Johannes Vierock & Johannes Oppermann & Jakob Walther & Dietmar Schmitz & David Owald & Andrew J, 2022. "Calcium-permeable channelrhodopsins for the photocontrol of calcium signalling," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35373-4
    DOI: 10.1038/s41467-022-35373-4
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