2023
Inflammation 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 Na
2021
Paclitaxel increases axonal localization and vesicular trafficking of Nav1.7
Akin EJ, Alsaloum M, Higerd GP, Liu S, Zhao P, Dib-Hajj FB, Waxman SG, Dib-Hajj SD. Paclitaxel increases axonal localization and vesicular trafficking of Nav1.7. Brain 2021, 144: 1727-1737. PMID: 33734317, PMCID: PMC8320304, DOI: 10.1093/brain/awab113.Peer-Reviewed Original ResearchConceptsDorsal root ganglion neuronsChemotherapy-induced peripheral neuropathyGanglion neuronsSensory axonsNav1.7 channelsPTX treatmentSensory neuronsHuman sensory neuronsEffect of paclitaxelSodium channel Nav1.7Chemotherapy drug paclitaxelAxonal vesicular transportConcentrations of paclitaxelNav1.7 mRNAInflammatory mediatorsNav1.7 expressionPeripheral neuropathyInflammatory milieuPrimary afferentsInflammatory conditionsChannel expressionChannel Nav1.7Nav1.7Increased expressionAxonal localization
2019
Building sensory axons: Delivery and distribution of NaV1.7 channels and effects of inflammatory mediators
Akin EJ, Higerd-Rusli GP, Mis MA, Tanaka BS, Adi T, Liu S, Dib-Hajj FB, Waxman SG, Dib-Hajj SD. Building sensory axons: Delivery and distribution of NaV1.7 channels and effects of inflammatory mediators. Science Advances 2019, 5: eaax4755. PMID: 31681845, PMCID: PMC6810356, DOI: 10.1126/sciadv.aax4755.Peer-Reviewed Original ResearchConceptsMicrotubule-dependent vesicular transportSingle-molecule resolutionVesicular traffickingVesicular transportSurface deliveryPlasma membraneMembrane distributionFunctional studiesAxon terminiSodium channel NaLive visualizationSensory axonsVesiclesTraffickingNew insightsChannel NaContribution of NaDisease statesRab6ANav1.7 channelsDorsal root ganglion neuronsTerminusThreefold increaseGanglion neuronsMembrane
2016
A painful neuropathy-associated Nav1.7 mutant leads to time-dependent degeneration of small-diameter axons associated with intracellular Ca2+ dysregulation and decrease in ATP levels
Rolyan H, Liu S, Hoeijmakers JG, Faber CG, Merkies IS, Lauria G, Black JA, Waxman SG. A painful neuropathy-associated Nav1.7 mutant leads to time-dependent degeneration of small-diameter axons associated with intracellular Ca2+ dysregulation and decrease in ATP levels. Molecular Pain 2016, 12: 1744806916674472. PMID: 27821467, PMCID: PMC5102167, DOI: 10.1177/1744806916674472.Peer-Reviewed Original ResearchConceptsSmall fiber neuropathySmall-diameter axonsTime-dependent degenerationDorsal root ganglion neuronsNerve fiber injuryNervous system disordersPrevious clinical reportsIntracellular calcium levelsMutant Nav1.7 channelsATP levelsAδ nerve fibersHigh altitude sicknessPainful neuropathyTime-dependent increaseFiber injuryClinical onsetGanglion neuronsOxygen species productionSystem disordersCalcium levelsClinical reportsDistal extremitiesIntracellular Ca2NeuropathyNav1.7 channels
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
2010
Slowly Progressive Axonal Degeneration in a Rat Model of Chronic, Nonimmune-Mediated Demyelination
Wilkins A, Kondo Y, Song J, Liu S, Compston A, Black J, Waxman S, Duncan I. Slowly Progressive Axonal Degeneration in a Rat Model of Chronic, Nonimmune-Mediated Demyelination. Journal Of Neuropathology & Experimental Neurology 2010, 69: 1256-1269. PMID: 21107138, DOI: 10.1097/nen.0b013e3181ffc317.Peer-Reviewed Original ResearchConceptsCentral nervous systemAxonal lossAxonal degenerationAxonal pathologyTrophic supportEarly axonal lossProgressive axonal lossProgressive axonal degenerationWhite matter tractsTaiep mutant ratNerve countsWild-type controlsChronic demyelinationNeurologic disabilityMyelin lossSignificant inflammationRat modelOligodendrocyte dysfunctionImmunohistochemical analysisTaiep ratsNervous systemCNS regionsAxonal transportMutant ratsOligodendrocyte lineage
2007
Exacerbation of experimental autoimmune encephalomyelitis after withdrawal of phenytoin and carbamazepine
Black JA, Liu S, Carrithers M, Carrithers LM, Waxman SG. Exacerbation of experimental autoimmune encephalomyelitis after withdrawal of phenytoin and carbamazepine. Annals Of Neurology 2007, 62: 21-33. PMID: 17654737, DOI: 10.1002/ana.21172.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnticonvulsantsAntigens, CDAxonsCarbamazepineCell CountDisease Models, AnimalEncephalomyelitis, Autoimmune, ExperimentalFlow CytometryGene Expression RegulationGlycoproteinsMiceMice, Inbred C57BLMyelin-Oligodendrocyte GlycoproteinNAV1.6 Voltage-Gated Sodium ChannelNerve Tissue ProteinsPeptide FragmentsPhenytoinPyramidal TractsSeverity of Illness IndexSodium ChannelsSubstance Withdrawal SyndromeConceptsExperimental autoimmune encephalomyelitisSodium channel blockersWithdrawal of phenytoinChannel blockersAutoimmune encephalomyelitisInflammatory infiltrateClinical studiesProtective effectMurine experimental autoimmune encephalomyelitisWithdrawal of carbamazepineCentral nervous system axonsCentral nervous systemAcute exacerbationAcute worseningClinical worseningEAE symptomsEAE miceNeuroinflammatory disordersClinical courseMyelin oligodendrocyteClinical statusControl miceMultiple sclerosisImmune cellsLong-term effects
2006
Long-term protection of central axons with phenytoin in monophasic and chronic-relapsing EAE
Black JA, Liu S, Hains BC, Saab CY, Waxman SG. Long-term protection of central axons with phenytoin in monophasic and chronic-relapsing EAE. Brain 2006, 129: 3196-3208. PMID: 16931536, DOI: 10.1093/brain/awl216.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAdministration, OralAnimalsAxonsCell CountCervical VertebraeChronic DiseaseEncephalomyelitis, Autoimmune, ExperimentalImmunohistochemistryInjections, SubcutaneousMiceMice, Inbred C57BLMyelin ProteinsMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinNeural ConductionPhenytoinRecurrenceSodium Channel BlockersSpinal CordTreatment OutcomeConceptsExperimental autoimmune encephalomyelitisC57/BL6 miceChronic-relapsing experimental autoimmune encephalomyelitisBL6 miceLong-term protectionAxonal degenerationClinical statusDays post-EAE inductionMurine experimental autoimmune encephalomyelitisLong-term protective effectPhenytoin-treated miceInflammatory cell infiltrationDorsal column axonsCompound action potentialSodium channel blockersAutoimmune encephalomyelitisAxonal lossPhenytoin treatmentUntreated miceNeuroinflammatory diseasesDorsal columnsMultiple sclerosisCNS injuryCell infiltrationCorticospinal tract
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 cellsSodium 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