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

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, Corinne Huchet, Céline Landon, Marco Canepari, Michel De Waard

Onderzoeksoutput: Articlepeer review

21 Citaten (Scopus)

Samenvatting

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.

Originele taal-2English
Artikelnummer417
Aantal pagina's13
TijdschriftNature communications
Volume13
Nummer van het tijdschrift1
DOI's
StatusPublished - 20 jan 2022

Bibliografische nota

© 2022. The Author(s).

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