Authors

Jérôme Montnach,1,2 Laila Ananda Blömer,2,3 Ludivine Lopez,1,2,4 Luiza Filipis,2,3 Hervé Meudal,5 Aude Lafoux,6 Sébastien Nicolas,1,2 Duong Chu,7 Cécile Caumes,4 Rémy Béroud,4 Chris Jopling,8 Frank Bosmans,9 Corinne Huchet,6 Céline Landon,5 Marco Canepari,2,3 and Michel De Waardcorresponding author1,2,4

Affiliations

"1l’institut du thorax, INSERM, CNRS, UNIV NANTES, F-44007 Nantes, France
2Laboratory of Excellence Ion Channels, Science & Therapeutics, F-06560 Valbonne, France
3Laboratoire Interdisciplinaire de Physique, Université Grenoble Alpes, CNRS UMR 5588, 38402 St Martin d’Hères, cedex France
4Smartox Biotechnology, 6 rue des Platanes, F-38120 Saint-Egrève, France
5Center for Molecular Biophysics, CNRS, rue Charles Sadron, CS 80054, Orléans, 45071 France
6Therassay Platform, IRS2-Université de Nantes, Nantes, France
7Queen’s University Faculty of Medicine, Kingston, ON Canada
8Institut de Génomique Fonctionnelle, 141 rue de la Cardonille, 34094 Montpellier, France
9Department of Basic and Applied Medical Sciences, Ghent University, Ghent, Belgium
Michel De Waard, Email: [email protected]
corresponding authorCorresponding author."

Topic

Biophotonics, Molecular Biology

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.

Subject terms: Sodium channels, Patch clamp

DOI: https://dx.doi.org/ 10.1038/s41467-022-27974-w

Extract

Illumination of samples was performed at 365 nm for different times (between 1 sec and 30 min illumination time) at 41.8 mW/cm2 or less (as specified in the Result section) for 10 min using a CoolLED pE4000 light source (CoolLED, UK).

Product Associated Features

The pE-4000 Universal Illumination System offers 16 selectable wavelengths from 365 - 770 nm, making it a highly flexible illuminator covering a wide variety of fluorophores

Product Type

pE-4000

Journal

Nature Communications

Year of Publication

2022

Country of Publication

UK