Genetically-encoded BRET probes shed light on ligand bias–induced variable ion selectivity in TRPV1 and P2X5/7
| dc.rights.license | open | en_US |
| hal.structure.identifier | Laboratoire de l'intégration, du matériau au système [IMS] | |
| dc.contributor.author | CHAPPE, Yann | |
| dc.contributor.author | PIERREDON, Sandra | |
| hal.structure.identifier | Laboratoire de l'intégration, du matériau au système [IMS] | |
| dc.contributor.author | JOUSHOMME, Alexandre | |
| hal.structure.identifier | Laboratoire de l'intégration, du matériau au système [IMS] | |
| dc.contributor.author | MOLLE, Pablo | |
| hal.structure.identifier | Laboratoire de l'intégration, du matériau au système [IMS] | |
| dc.contributor.author | GARENNE, André | |
| hal.structure.identifier | Laboratoire de l'intégration, du matériau au système [IMS] | |
| dc.contributor.author | CANOVI, Anne | |
| hal.structure.identifier | Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB] | |
| dc.contributor.author | BARBEAU, Solene | |
| hal.structure.identifier | Laboratoire de l'intégration, du matériau au système [IMS] | |
| dc.contributor.author | POULLETIER DE GANNES, Florence | |
| hal.structure.identifier | Laboratoire de l'intégration, du matériau au système [IMS] | |
| dc.contributor.author | HURTIER, Annabelle | |
| hal.structure.identifier | Laboratoire de l'intégration, du matériau au système [IMS] | |
| dc.contributor.author | LAGROYE, Isabelle | |
| hal.structure.identifier | Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB] | |
| dc.contributor.author | DUCRET, Thomas | |
| hal.structure.identifier | Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB] | |
| dc.contributor.author | QUIGNARD, Jean-François | |
| dc.contributor.author | COMPAN, Vincent | |
| hal.structure.identifier | Laboratoire de l'intégration, du matériau au système [IMS] | |
| dc.contributor.author | PERCHERANCIER, Yann
IDREF: 075934140 | |
| dc.date.accessioned | 2022-11-21T14:33:24Z | |
| dc.date.available | 2022-11-21T14:33:24Z | |
| dc.date.issued | 2022-11-07 | |
| dc.identifier.issn | 1091-6490 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/170333 | |
| dc.description.abstractEn | Whether ion channels experience ligand-dependent dynamic ion selectivity remains of critical importance since this could support ion channel functional bias. Tracking selective ion permeability through ion channels, however, remains challenging even with patch-clamp electrophysiology. In this study, we have developed highly sensitive bioluminescence resonance energy transfer (BRET) probes providing dynamic measurements of Ca2+ and K+ concentrations and ionic strength in the nanoenvironment of Transient Receptor Potential Vanilloid-1 Channel (TRPV1) and P2X channel pores in real time and in live cells during drug challenges. Our results indicate that AMG517, BCTC, and AMG21629, three well-known TRPV1 inhibitors, more potently inhibit the capsaicin (CAPS)-induced Ca2+ influx than the CAPS-induced K+ efflux through TRPV1. Even more strikingly, we found that AMG517, when injected alone, is a partial agonist of the K+ efflux through TRPV1 and triggers TRPV1-dependent cell membrane hyperpolarization. In a further effort to exemplify ligand bias in other families of cationic channels, using the same BRET-based strategy, we also detected concentration- and time-dependent ligand biases in P2X7 and P2X5 cationic selectivity when activated by benzoyl-adenosine triphosphate (Bz-ATP). These custom-engineered BRET-based probes now open up avenues for adding value to ion-channel drug discovery platforms by taking ligand bias into account. | |
| dc.description.sponsorship | Dépasser les limites des méthodes existantes de criblage à haut débit et de caractérisation des canaux ioniques grâce au transfert d'énergie en résonance de bioluminescence - ANR-19-CE44-0010 | en_US |
| dc.language.iso | EN | en_US |
| dc.rights | Attribution-NonCommercial-NoDerivs 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/us/ | * |
| dc.subject.en | Transient Receptor Potential Channels | |
| dc.subject.en | TRPV Cation Channels | |
| dc.subject.en | Ligands | |
| dc.subject.en | Capsaicin | |
| dc.subject.en | Energy Transfer | |
| dc.subject.en | Bias | |
| dc.title.en | Genetically-encoded BRET probes shed light on ligand bias–induced variable ion selectivity in TRPV1 and P2X5/7 | |
| dc.title.alternative | Proc Natl Acad Sci U S A | en_US |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1073/pnas.2205207119 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Biotechnologies | en_US |
| dc.identifier.pubmed | 36343259 | en_US |
| bordeaux.journal | Proceedings of the National Academy of Sciences of the United States of America | en_US |
| bordeaux.page | e2205207119 | en_US |
| bordeaux.volume | 119 | en_US |
| bordeaux.hal.laboratories | IMS : Laboratoire d’Intégration du Matériau au Système - UMR 5218 | en_US |
| bordeaux.issue | 46 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | Bordeaux INP | en_US |
| bordeaux.institution | CNRS | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| bordeaux.identifier.funderID | Conseil Régional Aquitaine | en_US |
| bordeaux.import.source | pubmed | |
| hal.export | false | |
| workflow.import.source | pubmed | |
| dc.rights.cc | Pas de Licence CC | en_US |
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