2023
Conserved but not critical: Trafficking and function of NaV1.7 are independent of highly conserved polybasic motifs
Tyagi S, Sarveswaran N, Higerd-Rusli G, Liu S, Dib-Hajj F, Waxman S, Dib-Hajj S. Conserved but not critical: Trafficking and function of NaV1.7 are independent of highly conserved polybasic motifs. Frontiers In Molecular Neuroscience 2023, 16: 1161028. PMID: 37008789, PMCID: PMC10060856, DOI: 10.3389/fnmol.2023.1161028.Peer-Reviewed Original ResearchSensory axonsPeripheral voltage-gated sodium channelsMajor unmet clinical needFunction of Nav1.7Non-addictive treatmentsUnmet clinical needVoltage-clamp recordingsVoltage-gated sodium channelsPain therapyChronic painPrimary afferentsNoxious stimuliTherapeutic modalitiesAction potentialsAxonal transportClinical needVesicular packagingSodium channelsHuman painPainAxonal traffickingAxonal surfaceAxonal membraneAxonsAttractive target
2021
Contributions of NaV1.8 and NaV1.9 to excitability in human induced pluripotent stem-cell derived somatosensory neurons
Alsaloum M, Labau JIR, Liu S, Estacion M, Zhao P, Dib-Hajj F, Waxman SG. Contributions of NaV1.8 and NaV1.9 to excitability in human induced pluripotent stem-cell derived somatosensory neurons. Scientific Reports 2021, 11: 24283. PMID: 34930944, PMCID: PMC8688473, DOI: 10.1038/s41598-021-03608-x.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAutopsyCell DifferentiationElectrophysiologyHumansImmunohistochemistryInduced Pluripotent Stem CellsMembrane PotentialsMutationNAV1.8 Voltage-Gated Sodium ChannelNAV1.9 Voltage-Gated Sodium ChannelNeuronsNeurosciencesPainPatch-Clamp TechniquesProtein IsoformsSensory Receptor CellsSomatosensory CortexConceptsNeuronal excitabilitySomatosensory neuronsPluripotent stem cell-derived sensory neuronsDynamic clamp electrophysiologyTreatment of painPromising novel modalityVoltage-gated sodium channelsSodium channel isoformsNeuronal membrane potentialGenetic knockout modelsNav1.9 currentsPharmacologic blockSensory neuronsNav1.8Cellular correlatesRepetitive firingClamp electrophysiologyExcitabilityNeuronal backgroundNovel modalityChannel isoformsSodium channelsNeuronsNav1.9Knockout models
2014
Contribution of sodium channels to lamellipodial protrusion and Rac1 and ERK1/2 activation in ATP‐stimulated microglia
Persson A, Estacion M, Ahn H, Liu S, Stamboulian‐Platel S, Waxman SG, Black JA. Contribution of sodium channels to lamellipodial protrusion and Rac1 and ERK1/2 activation in ATP‐stimulated microglia. Glia 2014, 62: 2080-2095. PMID: 25043721, DOI: 10.1002/glia.22728.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsAnimals, NewbornBrainCell MovementCells, CulturedEnzyme ActivationEnzyme InhibitorsGene Expression RegulationMembrane PotentialsMiceMice, TransgenicMicrogliaMitogen-Activated Protein Kinase 3NAV1.6 Voltage-Gated Sodium ChannelPseudopodiaRac1 GTP-Binding ProteinRatsRats, Sprague-DawleySignal TransductionSodium Channel BlockersConceptsActin-rich membrane protrusionsStream signaling cascadesAccumulation of Rac1Modulation of Rac1Sodium channel activityChannel activitySodium channelsP38α/βCellular polarizationMembrane protrusionsSignal transductionLamellipodial protrusionCellular pathwaysSignaling cascadesCoordinated processCytoskeletal elementsMembrane adhesionRac1Dependent pathwayPhosphorylated ERK1/2Central nervous systemATPERK1/2ATP stimulationActivated state
2012
Neuropathy‐associated NaV1.7 variant I228M impairs integrity of dorsal root ganglion neuron axons
Persson A, Liu S, Faber CG, Merkies IS, Black JA, Waxman SG. Neuropathy‐associated NaV1.7 variant I228M impairs integrity of dorsal root ganglion neuron axons. Annals Of Neurology 2012, 73: 140-145. PMID: 23280954, DOI: 10.1002/ana.23725.Peer-Reviewed Original ResearchConceptsSmall fiber neuropathyIntraepidermal nerve fibersIdiopathic small fiber neuropathyNa-Ca exchangeDRG neuronsNeurite lengthSensory axonsLoss of IENFsReverse Na-Ca exchangeDorsal root ganglion neuronsPeripheral sensory axonsPeripheral nerve axonsSodium channel blockers carbamazepineSodium channel activityAxonal degenerationGanglion neuronsSpontaneous firingNerve fibersAxonal integrityNeuron axonsImpaired regenerationNerve axonsFunction variantsAxonsSodium channels
2008
Sodium channel activity modulates multiple functions in microglia
Black JA, Liu S, Waxman SG. Sodium channel activity modulates multiple functions in microglia. Glia 2008, 57: 1072-1081. PMID: 19115387, DOI: 10.1002/glia.20830.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsAnimals, NewbornBrainCell MovementCell ProliferationCells, CulturedCoculture TechniquesCytokinesGliosisInflammation MediatorsMicrogliaNAV1.1 Voltage-Gated Sodium ChannelNAV1.5 Voltage-Gated Sodium ChannelNAV1.6 Voltage-Gated Sodium ChannelNerve Tissue ProteinsPhagocytosisPhenytoinRatsRats, Sprague-DawleySodium Channel BlockersSodium ChannelsTetrodotoxinConceptsIL-1 betaIL-1 alphaSodium channelsTNF-alphaPhagocytic activitySodium channel blockadeSodium channel Nav1.1Central nervous systemVoltage-gated sodium channelsSodium channel activitySodium channel isoformsActivated microgliaIL-10IL-6MCP-1Microglial migrationChannel Nav1.1Cultured microgliaIL-2IL-4MicroM TTXChannel blockadeMed miceMicrogliaTissue insult
2004
Contactin Associates with Sodium Channel Nav1.3 in Native Tissues and Increases Channel Density at the Cell Surface
Shah BS, Rush AM, Liu S, Tyrrell L, Black JA, Dib-Hajj SD, Waxman SG. Contactin Associates with Sodium Channel Nav1.3 in Native Tissues and Increases Channel Density at the Cell Surface. Journal Of Neuroscience 2004, 24: 7387-7399. PMID: 15317864, PMCID: PMC6729770, DOI: 10.1523/jneurosci.0322-04.2004.Peer-Reviewed Original ResearchConceptsAxotomized DRG neuronsDRG neuronsAxotomized dorsal root ganglion (DRG) neuronsDorsal root ganglion neuronsSodium channel Nav1.3Sodium channelsVoltage-gated sodium channelsHuman embryonic kidney 293 cellsNeuropathic painEmbryonic kidney 293 cellsGanglion neuronsSciatic nerveCell surfaceCell adhesion moleculeRat brainContactin/F3Kidney 293 cellsHEK-293 cellsAdhesion moleculesNeuronsElevated levelsSurface expressionContactinUpregulationCotransfected cellsChanges in the expression of tetrodotoxin‐sensitive sodium channels within dorsal root ganglia neurons in inflammatory pain
Black JA, Liu S, Tanaka M, Cummins TR, Waxman SG. Changes in the expression of tetrodotoxin‐sensitive sodium channels within dorsal root ganglia neurons in inflammatory pain. Pain 2004, 108: 237-247. PMID: 15030943, DOI: 10.1016/j.pain.2003.12.035.Peer-Reviewed Original ResearchMeSH KeywordsAnesthetics, LocalAnimalsBlotting, WesternCarrageenanCells, CulturedDisease Models, AnimalFunctional LateralityGanglia, SpinalGene Expression RegulationImmunohistochemistryIn Situ HybridizationInflammationMaleMembrane PotentialsNeuronsPainPatch-Clamp TechniquesRatsRats, Sprague-DawleyRNA, MessengerSodium ChannelsTetrodotoxinConceptsTTX-R currentsDorsal root gangliaDRG neuronsInflammatory painSodium channelsCarrageenan injectionProstaglandin E2TTX-R sodium channelsTetrodotoxin-sensitive sodium channelsDorsal root ganglion neuronsMultiple voltage-gated sodium channelsWhole-cell patch-clamp methodTTX-S sodium channelsTTX-R channelsTTX-S currentsSmall DRG neuronsInjection of carrageenanTTX-S channelsChronic inflammation resultsTetrodotoxin-resistant channelsVoltage-gated sodium channelsPatch-clamp methodUpregulation of mRNAAffected pawAcute administrationSodium channels contribute to microglia/macrophage activation and function in EAE and MS
Craner MJ, Damarjian TG, Liu S, Hains BC, Lo AC, Black JA, Newcombe J, Cuzner ML, Waxman SG. Sodium channels contribute to microglia/macrophage activation and function in EAE and MS. Glia 2004, 49: 220-229. PMID: 15390090, DOI: 10.1002/glia.20112.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsDisease Models, AnimalEncephalomyelitis, Autoimmune, ExperimentalFemaleGliosisMacrophagesMaleMiceMice, Inbred C57BLMicrogliaMultiple SclerosisNAV1.6 Voltage-Gated Sodium ChannelNerve DegenerationNerve Tissue ProteinsNeuroprotective AgentsPhagocytosisPhenytoinRNA, MessengerSodium Channel BlockersSodium ChannelsTetrodotoxinUp-RegulationConceptsExperimental autoimmune encephalomyelitisMultiple sclerosisSodium channel blockersSodium channelsMicroglial activationChannel blockersPhagocytic capacityMicroglia/macrophage activationSpecific sodium channel blockerAcute MS lesionsDirect neuroprotective effectsPhagocytosis of microgliaActivation of microgliaAnti-inflammatory mechanismsSodium channel-blocking drugsInflammatory cell infiltrateLoss of axonsDisease multiple sclerosisSodium channel blockadeChannel-blocking drugsAxonal sodium channelsAutoimmune encephalomyelitisInflammatory mechanismsNeuroinflammatory disordersCell infiltrate