2024
The evolution of patch-clamp electrophysiology: robotic, multiplex, and dynamic
Ghovanloo M, Dib-Hajj S, Waxman S. The evolution of patch-clamp electrophysiology: robotic, multiplex, and dynamic. Molecular Pharmacology 2024, 100001. PMID: 39164111, DOI: 10.1124/molpharm.124.000954.Peer-Reviewed Original ResearchPatch-clamp techniquePatch-clamp electrophysiologyPatch clampVoltage- and current-clamp modesIon channelsContribution of ion channelsCurrent-clamp modePatch-clamp methodOhm's lawDynamic-clampGating mechanisms of ion channelsMuscle cellsCardiac excitabilityGold standardExcitable cellsReceptorsGate conductionElectrophysiologyNeuronsElectrogenesisSimultaneous recordingCellsHigh-throughput automated platformMechanisms of ion channelsGating mechanismIon channels in osteoarthritis: emerging roles and potential targets
Zhou R, Fu W, Vasylyev D, Waxman S, Liu C. Ion channels in osteoarthritis: emerging roles and potential targets. Nature Reviews Rheumatology 2024, 20: 545-564. PMID: 39122910, DOI: 10.1038/s41584-024-01146-0.Peer-Reviewed Original ResearchIon channelsVoltage-dependent calcium channelsAcid-sensing ion channelsTransient receptor potential channelsVoltage-gated sodium channelsIon channel modulatorsFunction of ion channelsPotential clinical applicationsCalcium channelsPreclinical studiesClinical impactSymptomatic reliefPotassium channelsChloride channelsDisease-modifying treatmentsClinical trialsSodium channelsBone hyperplasiaChannel modulationIon channel biologySynovial inflammationClinical applicationPiezo channelsModel of OAPotential targetFunctionally-selective inhibition of threshold sodium currents and excitability in dorsal root ganglion neurons by cannabinol
Ghovanloo M, Effraim P, Tyagi S, Zhao P, Dib-Hajj S, Waxman S. Functionally-selective inhibition of threshold sodium currents and excitability in dorsal root ganglion neurons by cannabinol. Communications Biology 2024, 7: 120. PMID: 38263462, PMCID: PMC10805714, DOI: 10.1038/s42003-024-05781-x.Peer-Reviewed Original ResearchConceptsDorsal root ganglionDorsal root ganglion neuronal excitabilityDorsal root ganglion neuronsNeuronal excitabilityCurrent-clamp analysisSteady-state inactivationVoltage-dependent sodiumSlow inactivated stateAutomated patch clamp platformMultielectrode array recordingsNav currentsNeuropathic painSodium currentRoot ganglionGanglion neuronsSlow inactivationInactivated stateCurrent inhibitorsIon channelsNeuronsInhibitory effectCannabinolArray recordingsEndocannabinoidCannabinoidCompartment-specific regulation of NaV1.7 in sensory neurons after acute exposure to TNF-α
Tyagi S, Higerd-Rusli G, Ghovanloo M, Dib-Hajj F, Zhao P, Liu S, Kim D, Shim J, Park K, Waxman S, Choi J, Dib-Hajj S. Compartment-specific regulation of NaV1.7 in sensory neurons after acute exposure to TNF-α. Cell Reports 2024, 43: 113685. PMID: 38261513, PMCID: PMC10947185, DOI: 10.1016/j.celrep.2024.113685.Peer-Reviewed Original ResearchTNF-aSensory neuronsEffect of TNF-aSensory neuron excitabilityTumor necrosis factor-aRegulation of NaV1.7Voltage-gated sodiumPro-inflammatory cytokinesCompartment-specific effectsNeuronal plasma membraneSensitize nociceptorsNeuronal excitabilitySomatic membraneChannel N terminusElectrophysiological recordingsP38 MAPKIon channelsFactor AAcute exposureMolecular determinantsNeuronsAxonal endingsPhospho-acceptor sitesPlasma membraneCompartment-specific regulation
2023
Voltage-gated sodium channels (Na<sub>V</sub>) in GtoPdb v.2023.1
Catterall W, Goldin A, Waxman S. Voltage-gated sodium channels (NaV) in GtoPdb v.2023.1. IUPHAR/BPS Guide To Pharmacology CITE 2023, 2023 DOI: 10.2218/gtopdb/f82/2023.1.Peer-Reviewed Original ResearchTransmembrane segmentsLarge extracellular N-terminal domainSingle transmembrane segmentPotassium channel structureShort cytoplasmic domainFourth transmembrane segmentN-terminal domainExtracellular N-terminal domainSodium channelsMost excitable cellsNC-IUPHAR SubcommitteeGlutamate side chainCytoplasmic domainFatty acyl chainsHomologous domainsNovel structural featuresVoltage-gated sodium channelsShort selectivity filterSodium-selective ion channelsΒ-subunitChannel gatingSelectivity filterIon channelsSubunitsPore regionInflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat nociceptor activity
Higerd-Rusli G, Tyagi S, Baker C, Liu S, Dib-Hajj F, Dib-Hajj S, Waxman S. Inflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat nociceptor activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2215417120. PMID: 36897973, PMCID: PMC10089179, DOI: 10.1073/pnas.2215417120.Peer-Reviewed Original ResearchConceptsCell biological mechanismsAxonal surfaceLive-cell imagingIon channel traffickingAnterograde transport vesiclesTransport vesiclesInflammatory mediatorsChannel traffickingPlasma membraneVesicular loadingIon channelsKv channelsPotential therapeutic targetPotassium channel KSodium channel NaTraffickingBiological mechanismsTherapeutic targetAbundanceRetrograde transportDistal axonsChannel NaInflammatory painNociceptor activityAxonal transport
2022
The fates of internalized NaV1.7 channels in sensory neurons: Retrograde cotransport with other ion channels, axon-specific recycling, and degradation
Higerd-Rusli G, Tyagi S, Liu S, Dib-Hajj F, Waxman S, Dib-Hajj S. The fates of internalized NaV1.7 channels in sensory neurons: Retrograde cotransport with other ion channels, axon-specific recycling, and degradation. Journal Of Biological Chemistry 2022, 299: 102816. PMID: 36539035, PMCID: PMC9843449, DOI: 10.1016/j.jbc.2022.102816.Peer-Reviewed Original ResearchConceptsMembrane proteinsIon channelsNeuronal functionDistinct neuronal compartmentsAxonal membrane proteinsRetrograde traffickingNeuronal polarityRecycling pathwayLate endosomesPlasma membraneSpecific proteinsAxonal traffickingNovel mechanismCell membraneSodium channel NaNeuronal compartmentsMultiple pathwaysLive neuronsVoltage-gated sodium channel NaProteinEndocytosisMembrane specializationsTraffickingMembraneChannel NaPeripheral Ion Channel Genes Screening in Painful Small Fiber Neuropathy
Ślęczkowska M, Almomani R, Marchi M, Salvi E, de Greef B, Sopacua M, Hoeijmakers J, Lindsey P, Waxman S, Lauria G, Faber C, Smeets H, Gerrits M. Peripheral Ion Channel Genes Screening in Painful Small Fiber Neuropathy. International Journal Of Molecular Sciences 2022, 23: 14095. PMID: 36430572, PMCID: PMC9696564, DOI: 10.3390/ijms232214095.Peer-Reviewed Original ResearchConceptsSmall fiber neuropathyNeuropathic painIon channel genesPainful small fiber neuropathyPain score VASPathogenic heterozygous variantGenetic variantsIon channelsCohort studyDiabetic neuropathySevere painDifferent etiologiesPainPatientsVoltage-gated sodium ion channelsHeterozygous variantsNeuropathySodium ion channelsGene screeningGeneration sequencingPrevious findingsSuch variantsEtiologySCN1BVariantsNon-psychotropic phytocannabinoid interactions with voltage-gated sodium channels: An update on cannabidiol and cannabigerol
Ghovanloo M, Dib-Hajj S, Goodchild S, Ruben P, Waxman S. Non-psychotropic phytocannabinoid interactions with voltage-gated sodium channels: An update on cannabidiol and cannabigerol. Frontiers In Physiology 2022, 13: 1066455. PMID: 36439273, PMCID: PMC9691960, DOI: 10.3389/fphys.2022.1066455.Peer-Reviewed Original Research
2021
Voltage-gated sodium channels (Na<sub>V</sub>) in GtoPdb v.2021.3
Catterall W, Goldin A, Waxman S. Voltage-gated sodium channels (NaV) in GtoPdb v.2021.3. IUPHAR/BPS Guide To Pharmacology CITE 2021, 2021 DOI: 10.2218/gtopdb/f82/2021.3.Peer-Reviewed Original ResearchTransmembrane segmentsLarge extracellular N-terminal domainSingle transmembrane segmentPotassium channel structureShort cytoplasmic domainFourth transmembrane segmentN-terminal domainExtracellular N-terminal domainSodium channelsMost excitable cellsNC-IUPHAR SubcommitteeGlutamate side chainCytoplasmic domainFatty acyl chainsHomologous domainsNovel structural featuresVoltage-gated sodium channelsShort selectivity filterSodium-selective ion channelsΒ-subunitChannel gatingSelectivity filterIon channelsSubunitsPore region
2019
Voltage-gated sodium channels (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Catterall W, Goldin A, Waxman S. Voltage-gated sodium channels (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database. IUPHAR/BPS Guide To Pharmacology CITE 2019, 2019 DOI: 10.2218/gtopdb/f82/2019.4.Peer-Reviewed Original ResearchTransmembrane segmentsLarge extracellular N-terminal domainSingle transmembrane segmentPotassium channel structureShort cytoplasmic domainFourth transmembrane segmentN-terminal domainExtracellular N-terminal domainSodium channelsMost excitable cellsNC-IUPHAR SubcommitteeGlutamate side chainCytoplasmic domainFatty acyl chainsHomologous domainsNovel structural featuresShort selectivity filterVoltage-gated sodium channelsSodium-selective ion channelsΒ-subunitChannel gatingSelectivity filterIUPHAR/BPS GuideIon channelsSubunitsSodium Channels and Pain
Cummins T, Waxman S, Wood J. Sodium Channels and Pain. 2019, 233-262. DOI: 10.1093/oxfordhb/9780190860509.013.3.Peer-Reviewed Original ResearchSodium channel blockersPain conditionsChannel blockersSodium channelsAnalgesic drug targetsDifferent pain statesFunction Nav1.7 mutationsMost pain conditionsPeripheral sodium channelsSodium channel subtypesDamage-sensing neuronsDrug developmentVoltage-gated sodium channelsSodium channel isoformsDrug development programsIon channelsExcellent analgesicPain controlPain reliefPain statesNav1.7 mutationSodium-selective ion channelsNew analgesicsLocal anestheticsTherapeutic approaches
2017
THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Overview
Alexander S, Kelly E, Marrion N, Peters J, Faccenda E, Harding S, Pawson A, Sharman J, Southan C, Buneman O, Cidlowski J, Christopoulos A, Davenport A, Fabbro D, Spedding M, Striessnig J, Davies J, Collaborators C, Abbracchio M, Aldrich R, Al‐Hosaini K, Arumugam T, Attali B, Bäck M, Barnes N, Bathgate R, Beart P, Becirovic E, Bettler B, Biel M, Birdsall N, Blaho V, Boison D, Bräuner‐osborne H, Bröer S, Bryant C, Burnstock G, Calo G, Catterall W, Ceruti S, Chan S, Chandy K, Chazot P, Chiang N, Chun J, Chung J, Clapham D, Clapp L, Connor M, Cox H, Davies P, Dawson P, Decaen P, Dent G, Doherty P, Douglas S, Dubocovich M, Fong T, Fowler C, Frantz A, Fuller P, Fumagalli M, Futerman A, Gainetdinov R, Gershengorn M, Goldin A, Goldstein S, Goudet C, Gregory K, Grissmer S, Gundlach A, Hagenbuch B, Hamann J, Hammond, Hancox J, Hanson J, Hanukoglu I, Hay D, Hobbs A, Hollenberg A, Holliday N, Hoyer D, Ijzerman A, Inui K, Irving A, Ishii S, Jacobson K, Jan L, Jarvis M, Jensen R, Jockers R, Kaczmarek L, Kanai Y, Karnik S, Kellenberger S, Kemp S, Kennedy C, Kerr I, Kihara Y, Kukkonen J, Larhammar D, Leach K, Lecca D, Leeman S, Leprince J, Lolait S, Macewan D, Maguire J, Marshall F, Mazella J, Mcardle C, Michel M, Miller L, Mitolo V, Mizuno H, Monk P, Mouillac B, Murphy P, Nahon J, Nerbonne J, Nichols C, Norel X, Offermanns S, Palmer L, Panaro M, Papapetropoulos A, Perez‐reyes E, Pertwee R, Pintor S, Pisegna, Plant L, Poyner, Prossnitz E, Pyne S, Ramachandran R, Ren D, Rondard P, Ruzza C, Sackin H, Sanger G, Sanguinetti M, Schild L, Schiöth H, Schulte G, Schulz S, Segaloff D, Serhan C, Singh K, Slesinger P, Snutch T, Sobey C, Stewart G, Stoddart L, Summers R, Szabo C, Thwaites D, Toll L, Trimmer J, Tucker S, Vaudry H, Verri T, Vilargada J, Waldman, Ward D, Waxman S, Wei A, Willars G, Wong S, Woodruff T, Wulff H, Ye R, Yung Y, Zajac J. THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Overview. British Journal Of Pharmacology 2017, 174: s1-s16. PMID: 29055037, PMCID: PMC5650665, DOI: 10.1111/bph.13882.Peer-Reviewed Original ResearchConceptsBest available pharmacological toolsOfficial IUPHAR classificationAvailable pharmacological toolsDrug targetsIon channelsG protein-coupled receptorsHuman drug targetsLigand-gated ion channelsProtein-coupled receptorsVoltage-gated ion channelsNomenclature guidanceClinical pharmacologyCatalytic receptorsSelective pharmacologyOpen access knowledgebaseNuclear hormone receptorsPharmacological toolsHormone receptorsPrevious GuidesReceptorsLandscape formatPharmacologyBiennial publicationConcise guideRelated targets
2016
Voltage-Gated Ion Channels as Molecular Targets for Pain
Zamponi G, Han C, Waxman S. Voltage-Gated Ion Channels as Molecular Targets for Pain. 2016, 415-436. DOI: 10.1007/978-1-4899-7654-3_22.Peer-Reviewed Original ResearchVoltage-gated ion channelsDorsal root ganglion neuronsIon channelsMolecular targetsAction potential firing propertiesTreatment of painVoltage-gated sodiumImportant ion channelsNerve injuryGanglion neuronsPain signalingPeripheral afferentsPainFiring propertiesPharmacological modulatorsPotassium channelsTranslational researchDevelopment of modulatorsFunction changesHyperexcitabilityAfferentsInflammationMajor roleMajor themesInjury
2015
The Concise Guide to PHARMACOLOGY 2015/16: Overview
Alexander S, Kelly E, Marrion N, Peters J, Benson H, Faccenda E, Pawson A, Sharman J, Southan C, Buneman O, Catterall W, Cidlowski J, Davenport A, Fabbro D, Fan G, McGrath J, Spedding M, Davies J, Collaborators C, Aldrich R, Attali B, Bäck M, Barnes N, Bathgate R, Beart P, Becirovic E, Biel M, Birdsall N, Boison D, Bräuner‐Osborne H, Bröer S, Bryant C, Burnstock G, Burris T, Cain D, Calo G, Chan S, Chandy K, Chiang N, Christakos S, Christopoulos A, Chun J, Chung J, Clapham D, Connor M, Coons L, Cox H, Dautzenberg F, Dent G, Douglas S, Dubocovich M, Edwards D, Farndale R, Fong T, Forrest D, Fowler C, Fuller P, Gainetdinov R, Gershengorn M, Goldin A, Goldstein S, Grimm S, Grissmer S, Gundlach A, Hagenbuch B, Hammond, Hancox J, Hartig S, Hauger R, Hay D, Hébert T, Hollenberg A, Holliday N, Hoyer D, Ijzerman A, Inui K, Ishii S, Jacobson K, Jan L, Jarvis G, Jensen R, Jetten A, Jockers R, Kaczmarek L, Kanai Y, Kang H, Karnik S, Kerr I, Korach K, Lange C, Larhammar D, Leeb‐Lundberg F, Leurs R, Lolait S, Macewan D, Maguire J, May J, Mazella J, Mcardle C, Mcdonnell D, Michel M, Miller L, Mitolo V, Monie T, Monk P, Mouillac B, Murphy P, Nahon J, Nerbonne J, Nichols C, Norel X, Oakley R, Offermanns S, Palmer L, Panaro M, Perez‐Reyes E, Pertwee R, Pike J, Pin J, Pintor S, Plant L, Poyner, Prossnitz E, Pyne S, Ren D, Richer J, Rondard P, Ross R, Sackin H, Safi R, Sanguinetti M, Sartorius C, Segaloff D, Sladek F, Stewart G, Stoddart L, Striessnig J, Summers R, Takeda Y, Tetel M, Toll L, Trimmer J, Tsai M, Tsai S, Tucker S, Usdin T, Vilargada J, Vore M, Ward D, Waxman S, Webb P, Wei A, Weigel N, Willars G, Winrow C, Wong S, Wulff H, Ye R, Young M, Zajac J. The Concise Guide to PHARMACOLOGY 2015/16: Overview. British Journal Of Pharmacology 2015, 172: 5729-5743. PMID: 26650438, PMCID: PMC4718217, DOI: 10.1111/bph.13347.Peer-Reviewed Original ResearchConceptsBest available pharmacological toolsOfficial IUPHAR classificationAvailable pharmacological toolsDrug targetsIon channelsG protein-coupled receptorsHuman drug targetsLigand-gated ion channelsProtein-coupled receptorsVoltage-gated ion channelsNomenclature guidanceIUPHAR-DBMajor pharmacological targetCatalytic receptorsOpen access knowledgebaseNuclear hormone receptorsPharmacological targetsPharmacological toolsHormone receptorsNC-IUPHARPrevious GuidesReceptorsLandscape formatConcise guideRelated targets
2000
Do ‘demyelinating’ diseases involve more than myelin?
Waxman S. Do ‘demyelinating’ diseases involve more than myelin? Nature Medicine 2000, 6: 738-739. PMID: 10888913, DOI: 10.1038/77450.Peer-Reviewed Original Research
1995
Voltage-gated ion channels in axons: Localization, function, and development
WAXMAN S. Voltage-gated ion channels in axons: Localization, function, and development. 1995, 218-243. DOI: 10.1093/acprof:oso/9780195082937.003.0011.Peer-Reviewed Original Research
1994
Astrocyte Na+ channels are required for maintenance of Na+/K(+)-ATPase activity
Sontheimer H, Fernandez-Marques E, Ullrich N, Pappas C, Waxman S. Astrocyte Na+ channels are required for maintenance of Na+/K(+)-ATPase activity. Journal Of Neuroscience 1994, 14: 2464-2475. PMID: 8182422, PMCID: PMC6577452, DOI: 10.1523/jneurosci.14-05-02464.1994.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornAstrocytesAstrocytomaCell LineCells, CulturedElectrophysiologyGanglia, SpinalGliomaMembrane PotentialsModels, BiologicalOuabainRatsRats, Sprague-DawleyRubidiumSodiumSodium ChannelsSodium-Potassium-Exchanging ATPaseStrophanthidinTetrodotoxinTime FactorsTumor Cells, CulturedConceptsEffects of TTXGlial cellsAction potential electrogenesisRat spinal cordPatch-clamp recordingsAstrocyte membrane potentialDose-dependent mannerVoltage-activated channelsAcute blockadeSpinal cordVoltage-activated ion channelsSpecific blockerATPase activityAstrocytesTTXAstrocyte deathAction potentialsUnidirectional influxBlockadeExcitable cellsIon channelsOuabainExtracellular spaceMembrane potentialIon levels
1990
Ion channel organization of the myelinated fiber
Black J, Kocsis J, Waxman S. Ion channel organization of the myelinated fiber. Trends In Neurosciences 1990, 13: 48-54. PMID: 1690930, DOI: 10.1016/0166-2236(90)90068-l.Peer-Reviewed Original Research
1985
Organization of Ion Channels in the Myelinated Nerve Fiber
Waxman S, Ritchie J. Organization of Ion Channels in the Myelinated Nerve Fiber. Science 1985, 228: 1502-1507. PMID: 2409596, DOI: 10.1126/science.2409596.Peer-Reviewed Original Research