Canaux ioniques et douleur – IPMC

Recherche

Intranet

Thème

Physiologie moléculaire et physiopathologie des canaux ioniques

Physiopathologie des canaux Na+ et de l’excitabilité neuronale

Membres

Eric LINGUEGLIA

Chercheur INSERM

Enseignant-chercheur UniCA

Hélène LUBRANO DI SCAMPAMORTE

Valérie FRIEND

Véronique THIEFFIN

Présentation

Les douleurs chroniques affectent environ 20% des adultes et jusqu’à 50% de la population âgée. Cependant, les grandes familles d’antalgiques disponibles sont souvent d’une efficacité limitée et/ou possèdent une mauvaise tolérance, des effets secondaires importants ou des risques d’abus. Malgré cela, la thérapeutique médicamenteuse de la douleur n’a connu que peu d’innovations au cours des dernières années à cause d’une connaissance encore très incomplète de la physiopathologie associée. La découverte de nouvelles cibles moléculaires représente ainsi une réelle opportunité pour développer de nouvelles stratégies contre la douleur.

Parmi les senseurs moléculaires de la douleur récemment identifiés figurent les canaux ioniques ASIC (Acid Sensing Ion Channel), qui forment une classe de canaux cationiques dépolarisants excitateurs activés par les protons extracellulaires, et les canaux K2P, qui forment une classe de canaux potassiques hyperpolarisants inhibiteurs.

Le projet développé au sein de l’équipe a pour but d’étudier les propriétés et le rôle de ces canaux dans la douleur en combinant des approches de biologie moléculaire et cellulaire, d’électrophysiologie, de pharmacologie incluant la découverte et l’utilisation de peptides issus de venins et ciblant spécifiquement ces canaux, et des études de comportement chez l’animal.

Événements

31st Meeting of the French Society for Toxinology

Actualités

31st Meeting of the French Society for Toxinology : Toxins : Playing with and fighting them !

SFET : Société Française pour l’Etude des Toxines 31e meeting Hôtel Le Saint Paul, Nice – 1er et 2 décembre […]

Publications

Marchot P, Fajloun Z, Legros C, Benoit É, Diochot S, Report from the 29th Meeting on Toxinology, « Toxins: From the Wild to the Lab », Organized by the French Society of Toxinology on 30 November-1 December 2023., Toxins (Basel) 2024 Mar; 16(3): .

Negm A, Stobbe K, Ben Fradj S, Sanchez C, Landra-Willm A, Richter M, Fleuriot L, Debayle D, Deval E, Lingueglia E, Rovere C, Noel J, Acid-sensing ion channel 3 mediates pain hypersensitivity associated with high-fat diet consumption in mice., Pain 2024 Feb; 165(2): 470-486.

Mesirca P, Chemin J, Barrère C, Torre E, Gallot L, Monteil A, Bidaud I, Diochot S, Lazdunski M, Soong TW, Barrère-Lemaire S, Mangoni ME, Nargeot J, Selective blockade of Cav1.2 (α1C) versus Cav1.3 (α1D) L-type calcium channels by the black mamba toxin calciseptine., Nat Commun 2024 Jan; 15(1): 54.

Chafaï M, Delrocq A, Inquimbert P, Pidoux L, Delanoe K, Toft M, Brau F, Lingueglia E, Veltz R, Deval E, Dual contribution of ASIC1a channels in the spinal processing of pain information by deep projection neurons revealed by computational modeling., PLoS Comput Biol 2023 Apr; 19(4): e1010993.

Landra-Willm A, Karapurkar A, Duveau A, Chassot AA, Esnault L, Callejo G, Bied M, Häfner S, Lesage F, Wdziekonski B, Baron A, Fossat P, Marsollier L, Gasull X, Boué-Grabot E, Kienzler MA, Sandoz G, A photoswitchable inhibitor of TREK channels controls pain in wild-type intact freely moving animals., Nat Commun 2023 Mar; 14(1): 1160.

Khoury S, Colas J, Breuil V, Kosek E, Ahmed AS, Svensson CI, Marchand F, Deval E, Ferreira T, Identification of Lipid Biomarkers for Chronic Joint Pain Associated with Different Joint Diseases., Biomolecules 2023 Feb; 13(2): .

Marchot P, Benoit É, Fajloun Z, Diochot S, Report from the 28th Meeting on Toxinology, « Toxins: What’s up, Doc? », Organized by the French Society of Toxinology on 28-29 November 2022., Toxins (Basel) 2023 Feb; 15(2): .

Verkest C, Salinas M, Diochot S, Deval E, Lingueglia E, Baron A, Mechanisms of Action of the Peptide Toxins Targeting Human and Rodent Acid-Sensing Ion Channels and Relevance to Their In Vivo Analgesic Effects., Toxins (Basel) 2022 Oct; 14(10): .

Jacquot F, Khoury S, Labrum B, Delanoe K, Pidoux L, Barbier J, Delay L, Bayle A, Aissouni Y, Barriere DA, Kultima K, Freyhult E, Hugo A, Kosek E, Ahmed AS, Jurczak A, Lingueglia E, Svensson CI, Breuil V, Ferreira T, Marchand F, Deval E, Lysophosphatidylcholine 16:0 mediates chronic joint pain associated to rheumatic diseases through acid-sensing ion channel 3., Pain 2022 Oct; 163(10): 1999-2013.

Jurczak A, Delay L, Barbier J, Simon N, Krock E, Sandor K, Agalave NM, Rudjito R, Wigerblad G, Rogóż K, Briat A, Miot-Noirault E, Martinez-Martinez A, Brömme D, Grönwall C, Malmström V, Klareskog L, Khoury S, Ferreira T, Labrum B, Deval E, Jiménez-Andrade JM, Marchand F, Svensson CI, Antibody-induced pain-like behavior and bone erosion: links to subclinical inflammation, osteoclast activity, and acid-sensing ion channel 3-dependent sensitization., Pain 2022 Aug; 163(8): 1542-1559.

Ladant D, Marchot P, Diochot S, Prévost G, Popoff MR, Benoit E, Report from the 27th (Virtual) Meeting on Toxinology, « Toxins: Mr Hyde or Dr Jekyll? », Organized by the French Society of Toxinology, 9-10 December 2021., Toxins (Basel) 2022 Feb; 14(2): .

Pidoux L, Delanoe K, Barbier J, Marchand F, Lingueglia E, Deval E, Single Subcutaneous Injection of Lysophosphatidyl-Choline Evokes ASIC3-Dependent Increases of Spinal Dorsal Horn Neuron Activity., Front Mol Neurosci 2022 ; 15(): 880651.

Maatoug S, Cheikh A, Khamessi O, Tabka H, Landoulsi Z, Guigonis JM, Diochot S, Bendahhou S, Benkhalifa R, Cross Pharmacological, Biochemical and Computational Studies of a Human Kv3.1b Inhibitor from Androctonus australis Venom., Int J Mol Sci 2021 Nov; 22(22): .

Verkest C, Diochot S, Lingueglia E, Baron A, C-Jun N-Terminal Kinase Post-Translational Regulation of Pain-Related Acid-Sensing Ion Channels 1b and 3., J Neurosci 2021 Oct; 41(42): 8673-8685.

Ávalos Prado P, Landra-Willm A, Verkest C, Ribera A, Chassot AA, Baron A, Sandoz G, TREK channel activation suppresses migraine pain phenotype., iScience 2021 Sep; 24(9): 102961.

Verkest C, Häfner S, Ávalos Prado P, Baron A, Sandoz G, Migraine and Two-Pore-Domain Potassium Channels., Neuroscientist 2021 Jun; 27(3): 268-284.

Prieto M, Folci A, Poupon G, Schiavi S, Buzzelli V, Pronot M, François U, Pousinha P, Lattuada N, Abelanet S, Castagnola S, Chafai M, Khayachi A, Gwizdek C, Brau F, Deval E, Francolini M, Bardoni B, Humeau Y, Trezza V, Martin S, Missense mutation of Fmr1 results in impaired AMPAR-mediated plasticity and socio-cognitive deficits in mice., Nat Commun 2021 Mar; 12(1): 1557.

Salinas M, Kessler P, Douguet D, Sarraf D, Tonali N, Thai R, Servent D, Lingueglia E, Mambalgin-1 pain-relieving peptide locks the hinge between α4 and α5 helices to inhibit rat acid-sensing ion channel 1a., Neuropharmacology 2021 Mar; 185(): 108453.

Diochot S, Pain-related toxins in scorpion and spider venoms: a face to face with ion channels., J Venom Anim Toxins Incl Trop Dis 2021 ; 27(): e20210026.

Marchot P, Diochot S, Popoff MR, Benoit E, Report from the 26th Meeting on Toxinology, « Bioengineering of Toxins », Organized by the French Society of Toxinology (SFET) and Held in Paris, France, 4-5 December 2019., Toxins (Basel) 2020 Jan; 12(1): .

Nicolas S, Zoukimian C, Bosmans F, Montnach J, Diochot S, Cuypers E, De Waard S, Béroud R, Mebs D, Craik D, Boturyn D, Lazdunski M, Tytgat J, De Waard M, Chemical Synthesis, Proper Folding, Nav Channel Selectivity Profile and Analgesic Properties of the Spider Peptide Phlotoxin 1., Toxins (Basel) 2019 Jun; 11(6): .

Royal P, Andres-Bilbe A, Ávalos Prado P, Verkest C, Wdziekonski B, Schaub S, Baron A, Lesage F, Gasull X, Levitz J, Sandoz G, Migraine-Associated TRESK Mutations Increase Neuronal Excitability through Alternative Translation Initiation and Inhibition of TREK., Neuron 2019 Jan; 101(2): 232-245.e6.

Verkest C, Piquet E, Diochot S, Dauvois M, Lanteri-Minet M, Lingueglia E, Baron A, Effects of systemic inhibitors of acid-sensing ion channels 1 (ASIC1) against acute and chronic mechanical allodynia in a rodent model of migraine., Br J Pharmacol 2018 Nov; 175(21): 4154-4166.

Khayachi A, Gwizdek C, Poupon G, Alcor D, Chafai M, Cassé F, Maurin T, Prieto M, Folci A, De Graeve F, Castagnola S, Gautier R, Schorova L, Loriol C, Pronot M, Besse F, Brau F, Deval E, Bardoni B, Martin S, Sumoylation regulates FMRP-mediated dendritic spine elimination and maturation., Nat Commun 2018 Feb; 9(1): 757.

Besson T, Lingueglia E, Salinas M, Pharmacological modulation of Acid-Sensing Ion Channels 1a and 3 by amiloride and 2-guanidine-4-methylquinazoline (GMQ)., Neuropharmacology 2017 Oct; 125(): 429-440.

Aissouni Y, El Guerrab A, Hamieh AM, Ferrier J, Chalus M, Lemaire D, Grégoire S, Etienne M, Eschalier A, Ardid D, Lingueglia E, Marchand F, Acid-Sensing Ion Channel 1a in the amygdala is involved in pain and anxiety-related behaviours associated with arthritis., Sci Rep 2017 Mar; 7(): 43617.

Besson T, Debayle D, Diochot S, Salinas M, Lingueglia E, Low cost venom extractor based on Arduino(®) board for electrical venom extraction from arthropods and other small animals., Toxicon 2016 Aug; 118(): 156-61.

Diochot S, Alloui A, Rodrigues P, Dauvois M, Friend V, Aissouni Y, Eschalier A, Lingueglia E, Baron A, Analgesic effects of mambalgin peptide inhibitors of acid-sensing ion channels in inflammatory and neuropathic pain., Pain 2016 Mar; 157(3): 552-559.

Marra S, Ferru-Clément R, Breuil V, Delaunay A, Christin M, Friend V, Sebille S, Cognard C, Ferreira T, Roux C, Euller-Ziegler L, Noel J, Lingueglia E, Deval E, Non-acidic activation of pain-related Acid-Sensing Ion Channel 3 by lipids., EMBO J 2016 Feb; 35(4): 414-28.

Mourier G, Salinas M, Kessler P, Stura EA, Leblanc M, Tepshi L, Besson T, Diochot S, Baron A, Douguet D, Lingueglia E, Servent D, Mambalgin-1 Pain-relieving Peptide, Stepwise Solid-phase Synthesis, Crystal Structure, and Functional Domain for Acid-sensing Ion Channel 1a Inhibition., J Biol Chem 2016 Feb; 291(6): 2616-29.

Devader C, Moreno S, Roulot M, Deval E, Dix T, Morales CR, Mazella J, Increased Brain Neurotensin and NTSR2 Lead to Weak Nociception in NTSR3/Sortilin Knockout Mice., Front Neurosci 2016 ; 10(): 542.

Deval E, Lingueglia E, Acid-Sensing Ion Channels and nociception in the peripheral and central nervous systems., Neuropharmacology 2015 Jul; 94(): 49-57.

Baron A, Lingueglia E, Pharmacology of acid-sensing ion channels – Physiological and therapeutical perspectives., Neuropharmacology 2015 Jul; 94(): 19-35.

Lingueglia E, Lazdunski M, Acid-Sensing Ion Channels in the nervous system. Foreword., Neuropharmacology 2015 Jul; 94(): 1.

Loriol C, Cassé F, Khayachi A, Poupon G, Chafai M, Deval E, Gwizdek C, Martin S, mGlu5 receptors regulate synaptic sumoylation via a transient PKC-dependent diffusional trapping of Ubc9 into spines., Nat Commun 2014 Oct; 5(): 5113.

Salinas M, Besson T, Delettre Q, Diochot S, Boulakirba S, Douguet D, Lingueglia E, Binding site and inhibitory mechanism of the mambalgin-2 pain-relieving peptide on acid-sensing ion channel 1a., J Biol Chem 2014 May; 289(19): 13363-73.

Martin-Eauclaire MF, Bosmans F, Céard B, Diochot S, Bougis PE, A first exploration of the venom of the Buthus occitanus scorpion found in southern France., Toxicon 2014 Mar; 79(): 55-63.

Lingueglia E, [Acid-Sensing Ion Channels (ASICs) in pain]., Biol Aujourdhui 2014 ; 208(1): 13-20.

Baron A, Diochot S, Salinas M, Deval E, Noël J, Lingueglia E, Venom toxins in the exploration of molecular, physiological and pathophysiological functions of acid-sensing ion channels., Toxicon 2013 Dec; 75(): 187-204.

Alexander SP, Benson HE, Faccenda E, Pawson AJ, Sharman JL, McGrath JC, Catterall WA, Spedding M, Peters JA, Harmar AJ, , Abul-Hasn N, Anderson CM, Anderson CM, Araiksinen MS, Arita M, Arthofer E, Barker EL, Barratt C, Barnes NM, Bathgate R, Beart PM, Belelli D, Bennett AJ, Birdsall NJ, Boison D, Bonner TI, Brailsford L, Bröer S, Brown P, Calo G, Carter WG, Catterall WA, Chan SL, Chao MV, Chiang N, Christopoulos A, Chun JJ, Cidlowski J, Clapham DE, Cockcroft S, Connor MA, Cox HM, Cuthbert A, D..., The Concise Guide to PHARMACOLOGY 2013/14: overview., Br J Pharmacol 2013 Dec; 170(8): 1449-58.

Fromy B, Lingueglia E, Sigaudo-Roussel D, Saumet JL, Lazdunski M, [An ionic channel involved in the skin protection against pressure]., Med Sci (Paris) 2013 Feb; 29(2): 130-2.

Devilliers M, Busserolles J, Lolignier S, Deval E, Pereira V, Alloui A, Christin M, Mazet B, Delmas P, Noel J, Lazdunski M, Eschalier A, Activation of TREK-1 by morphine results in analgesia without adverse side effects., Nat Commun 2013 ; 4(): 2941.

Diochot S, Baron A, Salinas M, Douguet D, Scarzello S, Dabert-Gay AS, Debayle D, Friend V, Alloui A, Lazdunski M, Lingueglia E, Black mamba venom peptides target acid-sensing ion channels to abolish pain., Nature 2012 Oct; 490(7421): 552-5.

Delaunay A, Gasull X, Salinas M, Noël J, Friend V, Lingueglia E, Deval E, Human ASIC3 channel dynamically adapts its activity to sense the extracellular pH in both acidic and alkaline directions., Proc Natl Acad Sci U S A 2012 Aug; 109(32): 13124-9.

Fromy B, Lingueglia E, Sigaudo-Roussel D, Saumet JL, Lazdunski M, Asic3 is a neuronal mechanosensor for pressure-induced vasodilation that protects against pressure ulcers., Nat Med 2012 Aug; 18(8): 1205-7.

Deval E, Noël J, Gasull X, Delaunay A, Alloui A, Friend V, Eschalier A, Lazdunski M, Lingueglia E, Acid-sensing ion channels in postoperative pain., J Neurosci 2011 Apr; 31(16): 6059-66.

Deval E, Gasull X, Noël J, Salinas M, Baron A, Diochot S, Lingueglia E, Acid-sensing ion channels (ASICs): pharmacology and implication in pain., Pharmacol Ther 2010 Dec; 128(3): 549-58.

Noël J, Salinas M, Baron A, Diochot S, Deval E, Lingueglia E, Current perspectives on acid-sensing ion channels: new advances and therapeutic implications., Expert Rev Clin Pharmacol 2010 May; 3(3): 331-46.

Mazella J, Pétrault O, Lucas G, Deval E, Béraud-Dufour S, Gandin C, El-Yacoubi M, Widmann C, Guyon A, Chevet E, Taouji S, Conductier G, Corinus A, Coppola T, Gobbi G, Nahon JL, Heurteaux C, Borsotto M, Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design., PLoS Biol 2010 Apr; 8(4): e1000355.

Salinas M, Lazdunski M, Lingueglia E, Structural elements for the generation of sustained currents by the acid pain sensor ASIC3., J Biol Chem 2009 Nov; 284(46): 31851-9.

Noël J, Zimmermann K, Busserolles J, Deval E, Alloui A, Diochot S, Guy N, Borsotto M, Reeh P, Eschalier A, Lazdunski M, The mechano-activated K+ channels TRAAK and TREK-1 control both warm and cold perception., EMBO J 2009 May; 28(9): 1308-18.

Ettaiche M, Deval E, Pagnotta S, Lazdunski M, Lingueglia E, Acid-sensing ion channel 3 in retinal function and survival., Invest Ophthalmol Vis Sci 2009 May; 50(5): 2417-26.

Diochot S, Lazdunski M, Sea anemone toxins affecting potassium channels., Prog Mol Subcell Biol 2009 ; 46(): 99-122.

Deval E, Noël J, Lay N, Alloui A, Diochot S, Friend V, Jodar M, Lazdunski M, Lingueglia E, ASIC3, a sensor of acidic and primary inflammatory pain., EMBO J 2008 Nov; 27(22): 3047-55.

Baron A, Voilley N, Lazdunski M, Lingueglia E, Acid sensing ion channels in dorsal spinal cord neurons., J Neurosci 2008 Feb; 28(6): 1498-508.

Lingueglia E, Acid-sensing ion channels in sensory perception., J Biol Chem 2007 Jun; 282(24): 17325-9.

Ettaiche M, Deval E, Cougnon M, Lazdunski M, Voilley N, Silencing acid-sensing ion channel 1a alters cone-mediated retinal function., J Neurosci 2006 May; 26(21): 5800-9.

Lingueglia E, Deval E, Lazdunski M, FMRFamide-gated sodium channel and ASIC channels: a new class of ionotropic receptors for FMRFamide and related peptides., Peptides 2006 May; 27(5): 1138-52.

Deval E, Friend V, Thirant C, Salinas M, Jodar M, Lazdunski M, Lingueglia E, Regulation of sensory neuron-specific acid-sensing ion channel 3 by the adaptor protein Na+/H+ exchanger regulatory factor-1., J Biol Chem 2006 Jan; 281(3): 1796-807.

Deval E, Salinas M, Baron A, Lingueglia E, Lazdunski M, ASIC2b-dependent regulation of ASIC3, an essential acid-sensing ion channel subunit in sensory neurons via the partner protein PICK-1., J Biol Chem 2004 May; 279(19): 19531-9.

Diochot S, Baron A, Rash LD, Deval E, Escoubas P, Scarzello S, Salinas M, Lazdunski M, A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons., EMBO J 2004 Apr; 23(7): 1516-25.

Deval E, Baron A, Lingueglia E, Mazarguil H, Zajac JM, Lazdunski M, Effects of neuropeptide SF and related peptides on acid sensing ion channel 3 and sensory neuron excitability., Neuropharmacology 2003 Apr; 44(5): 662-71.

Baron A, Deval E, Salinas M, Lingueglia E, Voilley N, Lazdunski M, Protein kinase C stimulates the acid-sensing ion channel ASIC2a via the PDZ domain-containing protein PICK1., J Biol Chem 2002 Dec; 277(52): 50463-8.

Anzai N, Deval E, Schaefer L, Friend V, Lazdunski M, Lingueglia E, The multivalent PDZ domain-containing protein CIPP is a partner of acid-sensing ion channel 3 in sensory neurons., J Biol Chem 2002 May; 277(19): 16655-61.

Poët M, Tauc M, Lingueglia E, Cance P, Poujeol P, Lazdunski M, Counillon L, Exploration of the pore structure of a peptide-gated Na+ channel., EMBO J 2001 Oct; 20(20): 5595-602.

Baron A, Schaefer L, Lingueglia E, Champigny G, Lazdunski M, Zn2+ and H+ are coactivators of acid-sensing ion channels., J Biol Chem 2001 Sep; 276(38): 35361-7.

Sakai H, Lingueglia E, Champigny G, Mattei MG, Lazdunski M, Cloning and functional expression of a novel degenerin-like Na+ channel gene in mammals., J Physiol 1999 Sep; 519 Pt 2(Pt 2): 323-33.

Coscoy S, de Weille JR, Lingueglia E, Lazdunski M, The pre-transmembrane 1 domain of acid-sensing ion channels participates in the ion pore., J Biol Chem 1999 Apr; 274(15): 10129-32.

Darboux I, Lingueglia E, Pauron D, Barbry P, Lazdunski M, A new member of the amiloride-sensitive sodium channel family in Drosophila melanogaster peripheral nervous system., Biochem Biophys Res Commun 1998 May; 246(1): 210-6.

Darboux I, Lingueglia E, Champigny G, Coscoy S, Barbry P, Lazdunski M, dGNaC1, a gonad-specific amiloride-sensitive Na+ channel., J Biol Chem 1998 Apr; 273(16): 9424-9.

Coscoy S, Lingueglia E, Lazdunski M, Barbry P, The Phe-Met-Arg-Phe-amide-activated sodium channel is a tetramer., J Biol Chem 1998 Apr; 273(14): 8317-22.

Lingueglia E, de Weille JR, Bassilana F, Heurteaux C, Sakai H, Waldmann R, Lazdunski M, A modulatory subunit of acid sensing ion channels in brain and dorsal root ganglion cells., J Biol Chem 1997 Nov; 272(47): 29778-83.

Lingueglia E, Champigny G, Lazdunski M, Barbry P, Cloning of the amiloride-sensitive FMRFamide peptide-gated sodium channel., Nature 1995 Dec; 378(6558): 730-3.