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

• DOI: 10.1038/s41467-022-27974-w
• Publication Date: 2022-01-20T11:05:12Z
• Authors: 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
• Keywords: HEK 293 cells; Ex vivo

Abstract Photoactivatable drugs targeting ligand-gated ion channels open up new opportunities for light-guided therapeutic interventions. Photoactivable toxins 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 photoactivatable peptide that targets voltage-gated sodium (Na V ) validate its activity in vitro HEK293 cells, ex vivo brain slices on mice neuromuscular junctions. We find HwTxIV-Nvoc enables precise of neuronal Na channel function under all conditions tested. By creating multiple toxins, demonstrate broad applicability this toxin-photoactivation technology.