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Genetically-encoded BRET probes shed light on ligand bias–induced variable ion selectivity in TRPV1 and P2X5/7

dc.rights.licenseopenen_US
hal.structure.identifierLaboratoire de l'intégration, du matériau au système [IMS]
dc.contributor.authorCHAPPE, Yann
dc.contributor.authorPIERREDON, Sandra
hal.structure.identifierLaboratoire de l'intégration, du matériau au système [IMS]
dc.contributor.authorJOUSHOMME, Alexandre
hal.structure.identifierLaboratoire de l'intégration, du matériau au système [IMS]
dc.contributor.authorMOLLE, Pablo
hal.structure.identifierLaboratoire de l'intégration, du matériau au système [IMS]
dc.contributor.authorGARENNE, André
hal.structure.identifierLaboratoire de l'intégration, du matériau au système [IMS]
dc.contributor.authorCANOVI, Anne
hal.structure.identifierCentre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
dc.contributor.authorBARBEAU, Solene
hal.structure.identifierLaboratoire de l'intégration, du matériau au système [IMS]
dc.contributor.authorPOULLETIER DE GANNES, Florence
hal.structure.identifierLaboratoire de l'intégration, du matériau au système [IMS]
dc.contributor.authorHURTIER, Annabelle
hal.structure.identifierLaboratoire de l'intégration, du matériau au système [IMS]
dc.contributor.authorLAGROYE, Isabelle
hal.structure.identifierCentre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
dc.contributor.authorDUCRET, Thomas
hal.structure.identifierCentre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
dc.contributor.authorQUIGNARD, Jean-François
dc.contributor.authorCOMPAN, Vincent
hal.structure.identifierLaboratoire de l'intégration, du matériau au système [IMS]
dc.contributor.authorPERCHERANCIER, Yann
IDREF: 075934140
dc.date.accessioned2022-11-21T14:33:24Z
dc.date.available2022-11-21T14:33:24Z
dc.date.issued2022-11-07
dc.identifier.issn1091-6490en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/170333
dc.description.abstractEnWhether 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.sponsorshipDépasser 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-CE44-0010en_US
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subject.enTransient Receptor Potential Channels
dc.subject.enTRPV Cation Channels
dc.subject.enLigands
dc.subject.enCapsaicin
dc.subject.enEnergy Transfer
dc.subject.enBias
dc.title.enGenetically-encoded BRET probes shed light on ligand bias–induced variable ion selectivity in TRPV1 and P2X5/7
dc.title.alternativeProc Natl Acad Sci U S Aen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1073/pnas.2205207119en_US
dc.subject.halSciences du Vivant [q-bio]/Biotechnologiesen_US
dc.identifier.pubmed36343259en_US
bordeaux.journalProceedings of the National Academy of Sciences of the United States of Americaen_US
bordeaux.pagee2205207119en_US
bordeaux.volume119en_US
bordeaux.hal.laboratoriesIMS : Laboratoire d’Intégration du Matériau au Système - UMR 5218en_US
bordeaux.issue46en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionBordeaux INPen_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDConseil Régional Aquitaineen_US
bordeaux.import.sourcepubmed
hal.exportfalse
workflow.import.sourcepubmed
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20of%20the%20United%20States%20of%20America&rft.date=2022-11-07&rft.volume=119&rft.issue=46&rft.spage=e2205207119&rft.epage=e2205207119&rft.eissn=1091-6490&rft.issn=1091-6490&rft.au=CHAPPE,%20Yann&PIERREDON,%20Sandra&JOUSHOMME,%20Alexandre&MOLLE,%20Pablo&GARENNE,%20Andr%C3%A9&rft.genre=article


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