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
Abstract
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 (Na V ) 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 Na V channel function under all conditions tested. By creating multiple photoactivatable toxins, we demonstrate the broad applicability of this toxin-photoactivation technology.