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In vivo spatiotemporal control of voltage-gated ion channels by using photoactivatable peptidic toxins

Author

Listed:
  • Jérôme Montnach

    (l’institut du thorax, INSERM, CNRS, UNIV NANTES
    Laboratory of Excellence Ion Channels, Science & Therapeutics)

  • Laila Ananda Blömer

    (Laboratory of Excellence Ion Channels, Science & Therapeutics
    Université Grenoble Alpes, CNRS UMR 5588)

  • Ludivine Lopez

    (l’institut du thorax, INSERM, CNRS, UNIV NANTES
    Laboratory of Excellence Ion Channels, Science & Therapeutics
    Smartox Biotechnology)

  • Luiza Filipis

    (Laboratory of Excellence Ion Channels, Science & Therapeutics
    Université Grenoble Alpes, CNRS UMR 5588)

  • Hervé Meudal

    (Center for Molecular Biophysics, CNRS, rue Charles Sadron, CS 80054)

  • Aude Lafoux

    (Therassay Platform, IRS2-Université de Nantes)

  • Sébastien Nicolas

    (l’institut du thorax, INSERM, CNRS, UNIV NANTES
    Laboratory of Excellence Ion Channels, Science & Therapeutics)

  • Duong Chu

    (Queen’s University Faculty of Medicine)

  • Cécile Caumes

    (Smartox Biotechnology)

  • Rémy Béroud

    (Smartox Biotechnology)

  • Chris Jopling

    (Institut de Génomique Fonctionnelle)

  • Frank Bosmans

    (Ghent University)

  • Corinne Huchet

    (Therassay Platform, IRS2-Université de Nantes)

  • Céline Landon

    (Center for Molecular Biophysics, CNRS, rue Charles Sadron, CS 80054)

  • Marco Canepari

    (Laboratory of Excellence Ion Channels, Science & Therapeutics
    Université Grenoble Alpes, CNRS UMR 5588)

  • Michel Waard

    (l’institut du thorax, INSERM, CNRS, UNIV NANTES
    Laboratory of Excellence Ion Channels, Science & Therapeutics
    Smartox Biotechnology)

Abstract

Photoactivatable drugs targeting ligand-gated ion channels open up new opportunities for light-guided therapeutic interventions. Photoactivable toxins targeting ion channels have the potential to control excitable cell activities with low invasiveness and high spatiotemporal precision. As proof-of-concept, we develop HwTxIV-Nvoc, a UV light-cleavable and photoactivatable peptide that targets voltage-gated sodium (NaV) channels and validate its activity in vitro in HEK293 cells, ex vivo in brain slices and in vivo on mice neuromuscular junctions. We find that HwTxIV-Nvoc enables precise spatiotemporal control of neuronal NaV channel function under all conditions tested. By creating multiple photoactivatable toxins, we demonstrate the broad applicability of this toxin-photoactivation technology.

Suggested Citation

  • Jérôme Montnach & Laila Ananda Blömer & Ludivine Lopez & Luiza Filipis & Hervé Meudal & Aude Lafoux & Sébastien Nicolas & Duong Chu & Cécile Caumes & Rémy Béroud & Chris Jopling & Frank Bosmans & Cori, 2022. "In vivo spatiotemporal control of voltage-gated ion channels by using photoactivatable peptidic toxins," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-27974-w
    DOI: 10.1038/s41467-022-27974-w
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