In vivo spatiotemporal control of voltage-gated ion channels by using photoactivatable peptidic toxins
- Others:
- Institut du Thorax [Nantes]
- Institut de pharmacologie moléculaire et cellulaire (IPMC) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UniCA)
- Laboratoire Interdisciplinaire de Physique [Saint Martin d'Hères] (LIPhy) ; Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
- Smartox Biotechnology
- Centre de biophysique moléculaire (CBM) ; Université d'Orléans (UO)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)
- Université de Nantes (UN)
- Queen's University [Kingston, Canada]
- Institut de Génomique Fonctionnelle (IGF) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
- Universiteit Gent = Ghent University (UGENT)
- M. De Waard and M. Canepari thank the Agence Nationale de la Recherche (ANR) for financial support to the laboratory of excellence "Ion Channels, Science and Therapeutics" (grant N° ANR-11-LABX-0015). Both researchers also thank the ANR for a grant entitled OptChemCom (grant N° ANR-18-CE19-0024-02). This work was supported by the Fondation Leducq in the frame of its program of ERPT equipment support (purchase of an automated patch-clamp system), by a grant "New Team" of the Région Pays de la Loire to M. De Waard, the National Institutes of Health (R01NS091352 to F.B.), by an AFM grant for LED equipment (AFM22401) and by a European FEDER grant in support of the automated patch-clamp system of Nanion. The salary of S. Nicolas was supported by the Fondation Leducq. The fellowships of J. Montnach and L. Filipis are provided by the ANR OptChemCom. The scholarship of L.A. Blömer is provided by the laboratory of excellence "Ion Channels, Science and Therapeutics".
- ANR-18-CE19-0024,OptChemCom,Technologies intégrées d' optique, photochimie et informatique pour étudier la synergie physiologique des canaux ioniques(2018)
Description
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.
Abstract
International audience
Additional details
- URL
- https://hal.science/hal-03578128
- URN
- urn:oai:HAL:hal-03578128v1
- Origin repository
- UNICA