2024
Interplay of Nav1.8 and Nav1.7 channels drives neuronal hyperexcitability in neuropathic pain
Vasylyev D, Zhao P, Schulman B, Waxman S. Interplay of Nav1.8 and Nav1.7 channels drives neuronal hyperexcitability in neuropathic pain. The Journal Of General Physiology 2024, 156: e202413596. PMID: 39378238, PMCID: PMC11465073, DOI: 10.1085/jgp.202413596.Peer-Reviewed Original ResearchConceptsDorsal root ganglionGain-of-function Nav1.7 mutationsDorsal root ganglion neuronsSodium channel Nav1.7Inherited erythromelalgiaNav1.7 mutationsNeuropathic painNeuronal hyperexcitabilityOpen-probabilityVoltage-gated sodium channel Nav1.7Hyperexcitability of DRG neuronsModel of neuropathic painSubthreshold membrane potential oscillationsResting membrane potentialMembrane potential oscillationsReduced firing probabilityIncreased rheobaseNav1.8 channelsDRG neuronsHuman genetic modelsNav1.8Root ganglionNav1.7 channelsNav1.7AP generation
2023
Ih current stabilizes excitability in rodent DRG neurons and reverses hyperexcitability in a nociceptive neuron model of inherited neuropathic pain
Vasylyev D, Liu S, Waxman S. Ih current stabilizes excitability in rodent DRG neurons and reverses hyperexcitability in a nociceptive neuron model of inherited neuropathic pain. The Journal Of Physiology 2023, 601: 5341-5366. PMID: 37846879, PMCID: PMC10843455, DOI: 10.1113/jp284999.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsErythromelalgiaGanglia, SpinalHumansNAV1.7 Voltage-Gated Sodium ChannelNeuralgiaNeuronsNociceptorsRodentiaConceptsFunction Nav1.7 mutationsDorsal root ganglion neuronsSmall DRG neuronsDRG neuronsNav1.7 mutationNeuropathic painGanglion neuronsHuman genetic modelsAction potentialsDRG neuron excitabilityDRG neuron hyperexcitabilityRodent DRG neuronsAP generationCardiac cellsPotential molecular targetsNeuron hyperexcitabilitySevere painPain therapeuticsCNS neuronsExcessive firingNeuron excitabilityCentral neuronsSubthreshold oscillationsHyperexcitabilityNeuronal firing
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 ResearchMeSH KeywordsAction PotentialsAxonsHumansIon ChannelsMembrane ProteinsNAV1.7 Voltage-Gated Sodium ChannelSensory Receptor CellsConceptsMembrane 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
2019
A gain-of-function sodium channel β2-subunit mutation in painful diabetic neuropathy
Alsaloum M, Estacion M, Almomani R, Gerrits MM, Bönhof GJ, Ziegler D, Malik R, Ferdousi M, Lauria G, Merkies IS, Faber CG, Dib-Hajj S, Waxman S. A gain-of-function sodium channel β2-subunit mutation in painful diabetic neuropathy. Molecular Pain 2019, 15: 1744806919849802. PMID: 31041876, PMCID: PMC6510061, DOI: 10.1177/1744806919849802.Peer-Reviewed Original ResearchConceptsDiabetic peripheral neuropathyPeripheral neuropathyNeuropathic painDiabetic peripheral neuropathy patientsPainful diabetic peripheral neuropathyDorsal root ganglion neuronsPainful diabetic neuropathyPeripheral neuropathy patientsSodium channel β subunitsSpectrum of patientsUse-dependent inhibitionCardiac conducting systemSodium channel α subunitVoltage-gated sodium channelsChannel α-subunitsSCN11A geneDiabetic neuropathyDiabetes mellitusChronic painNeuropathy patientsGanglion neuronsNegative genetic screeningChannel β subunitHealth sequelaeRepetitive stimulation
2018
Nonmuscle myosin II isoforms interact with sodium channel alpha subunits
Dash B, Han C, Waxman S, Dib-Hajj S. Nonmuscle myosin II isoforms interact with sodium channel alpha subunits. Molecular Pain 2018, 14: 1744806918788638. PMID: 29956586, PMCID: PMC6052497, DOI: 10.1177/1744806918788638.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAnkyrinsBrainCell Line, TransformedElectric StimulationGanglia, SpinalGene Expression RegulationGreen Fluorescent ProteinsHumansImmunoprecipitationMiceMice, Inbred C57BLMice, TransgenicMolecular Motor ProteinsMyosin Heavy ChainsNAV1.6 Voltage-Gated Sodium ChannelNonmuscle Myosin Type IIBPatch-Clamp TechniquesRatsTransfectionConceptsSodium channel alpha subunitND7/23 cellsChannel alpha subunitDorsal root ganglion tissueAlpha subunitMyosin II motor proteinsNonmuscle myosin II isoformsRodent nervous tissueRodent brain tissueSteady-state fast inactivationVoltage-sensitive channelsFast inactivationVoltage-dependent activationSodium channel alphaGanglion tissueIsoform-dependent mannerMyosin II isoformsNervous tissueRecombinant myosinBrain tissueCommon structural motifRamp currentsMotor proteinsCellular excitabilitySodium channels
2016
Pharmacotherapy for Pain in a Family With Inherited Erythromelalgia Guided by Genomic Analysis and Functional Profiling
Geha P, Yang Y, Estacion M, Schulman BR, Tokuno H, Apkarian AV, Dib-Hajj SD, Waxman SG. Pharmacotherapy for Pain in a Family With Inherited Erythromelalgia Guided by Genomic Analysis and Functional Profiling. JAMA Neurology 2016, 73: 659. PMID: 27088781, DOI: 10.1001/jamaneurol.2016.0389.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAdultAnalgesics, Non-NarcoticBrainCarbamazepineChronic PainDNA Mutational AnalysisDouble-Blind MethodElectric StimulationErythromelalgiaFemaleGanglia, SpinalHumansMagnetic Resonance ImagingMaleMutationNAV1.7 Voltage-Gated Sodium ChannelPain MeasurementRegression AnalysisSensory Receptor CellsConceptsMean episode durationDRG neuronsPatient 1Nav1.7 mutationEpisode durationDorsal root ganglion neuronsPlacebo-controlled studyMaintenance periodAttenuation of painEffects of carbamazepineBrain activityFunctional magnetic resonance imagingMagnetic resonance imagingT mutationMutant channelsFunctional magnetic resonanceNeuropathic painSecondary somatosensoryChronic painPain areaPatient 2Ganglion neuronsEffective pharmacotherapyNight awakeningsPlacebo
2012
Structural modelling and mutant cycle analysis predict pharmacoresponsiveness of a Nav1.7 mutant channel
Yang Y, Dib-Hajj SD, Zhang J, Zhang Y, Tyrrell L, Estacion M, Waxman SG. Structural modelling and mutant cycle analysis predict pharmacoresponsiveness of a Nav1.7 mutant channel. Nature Communications 2012, 3: 1186. PMID: 23149731, PMCID: PMC3530897, DOI: 10.1038/ncomms2184.Peer-Reviewed Original Research
2008
Nav1.9, G‐proteins, and nociceptors
Waxman SG, Estacion M. Nav1.9, G‐proteins, and nociceptors. The Journal Of Physiology 2008, 586: 917-918. PMID: 18287383, PMCID: PMC2375642, DOI: 10.1113/jphysiol.2007.149922.Peer-Reviewed Original Research
2007
A case of inherited erythromelalgia
Novella SP, Hisama FM, Dib-Hajj SD, Waxman SG. A case of inherited erythromelalgia. Nature Reviews Neurology 2007, 3: 229-234. PMID: 17410110, DOI: 10.1038/ncpneuro0425.Peer-Reviewed Original ResearchConceptsLaboratory blood testingMRI brain scansNeuropathic painSymptomatic managementNeurological examinationRecurrent episodesBlood testingMedical historySkin biopsiesFamily historyDistal extremitiesBrain scansSimilar symptomsGenetic counselingEarly childhoodPainEpisodesErythromelalgiaBiopsyErythemaSymptomsExtremitiesDNA analysis
2006
Axonal conduction and injury in multiple sclerosis: the role of sodium channels
Waxman SG. Axonal conduction and injury in multiple sclerosis: the role of sodium channels. Nature Reviews Neuroscience 2006, 7: 932-941. PMID: 17115075, DOI: 10.1038/nrn2023.Peer-Reviewed Original ResearchConceptsAxonal degenerationSodium channelsChannel isoformsDistinct pathophysiological rolesKey PointsMultiple sclerosisMultiple neurological deficitsRelapsing-remitting courseRestoration of conductionDegeneration of axonsCerebellar Purkinje neuronsVoltage-gated sodium channelsContext of demyelinationNeurological deficitsProgressive courseMultiple sclerosisAxonal conductionDisease progressionNav1.8 channelsConduction failurePathophysiological rolePurkinje neuronsCNS axonsFiring patternsLoss of coordinationAberrant expression
2001
Transcriptional channelopathies: An emerging class of disorders
Waxman S. Transcriptional channelopathies: An emerging class of disorders. Nature Reviews Neuroscience 2001, 2: 652-659. PMID: 11533733, DOI: 10.1038/35090026.Peer-Reviewed Original ResearchConceptsNerve injuryMultiple sclerosisSodium channel geneTranscriptional channelopathiesChannel transcriptionPeripheral nerve injurySpinal sensory neuronsChannel genesExperimental nerve injuryFamily of disordersAction potential conductionAutoimmune channelopathiesDemyelinated nervesNeuropathic painDemyelinating conditionMotor abnormalitiesNeurotrophic factorClass of disordersSensory neuronsCalcium channelsChannel expressionCerebellar ataxiaPurkinje cellsPotential conductionChannelopathiesContribution of Nav1.8 Sodium Channels to Action Potential Electrogenesis in DRG Neurons
Renganathan M, Cummins T, Waxman S. Contribution of Nav1.8 Sodium Channels to Action Potential Electrogenesis in DRG Neurons. Journal Of Neurophysiology 2001, 86: 629-640. PMID: 11495938, DOI: 10.1152/jn.2001.86.2.629.Peer-Reviewed Original ResearchConceptsAction potential electrogenesisDRG neuronsSodium channelsAction potentialsTTX-R sodium channelsSodium-dependent action potentialsDorsal root ganglion neuronsMultiple sodium channelsSmall DRG neuronsCurrent-clamp recordingsNav1.8 sodium channelsSignificant differencesSteady-state inactivationAction potential overshootMaximum rise slopeMV/msAction potential productionFast TTXGanglion neuronsModest depolarizationNeuronsInput resistanceMembrane depolarizationInward membraneElectrogenesis
2000
The neuron as a dynamic electrogenic machine: modulation of sodiumchannel expression as a basis for functional plasticity in neurons
Waxman S. The neuron as a dynamic electrogenic machine: modulation of sodiumchannel expression as a basis for functional plasticity in neurons. Philosophical Transactions Of The Royal Society B Biological Sciences 2000, 355: 199-213. PMID: 10724456, PMCID: PMC1692729, DOI: 10.1098/rstb.2000.0559.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsElectric ConductivityGene ExpressionNeuronal PlasticityNeuronsSodium ChannelsConceptsSodium channelsMammalian nervous systemSodium channel geneNervous systemDozen genesDistinct sodium channelsVoltage-gated sodium channelsGenesElectrogenic machineryNormal nervous systemSodium channel expressionFunctional plasticityMembrane of neuronsAction potential activityTranscriptionPathological insultsPhysiological inputsMost neuronsCrucial roleExpressionNeuronsFunctional propertiesElectroresponsive propertiesPotential activityMachinery
1998
Axon Conduction and Survival in CNS White Matter During Energy Deprivation: A Developmental Study
Fern R, Davis P, Waxman S, Ransom B. Axon Conduction and Survival in CNS White Matter During Energy Deprivation: A Developmental Study. Journal Of Neurophysiology 1998, 79: 95-105. PMID: 9425180, DOI: 10.1152/jn.1998.79.1.95.Peer-Reviewed Original ResearchConceptsAnoxia/aglycemiaCompound action potentialWithdrawal of oxygenOptic nerveCNS white matterWhite matterIsolated rat optic nerveEvoked compound action potentialAdult optic nerveOptic nerve functionRat optic nervePostnatal day 10Permanent lossMin of glucoseEnergy deprivationWithdrawal of glucoseGlucose withdrawalNerve functionAstrocytic glycogenAxon conductionHeightened metabolic activityAdult ratsAglycemiaIrreversible injuryNerveResistance to anoxic injury in the dorsal columns of adult rat spinal cord following demyelination
Imaizumi T, Kocsis J, Waxman S. Resistance to anoxic injury in the dorsal columns of adult rat spinal cord following demyelination. Brain Research 1998, 779: 292-296. PMID: 9473700, DOI: 10.1016/s0006-8993(97)01171-2.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsDemyelinating DiseasesFemaleHypoxiaNeural ConductionRatsRats, WistarSpinal Cord DiseasesConceptsCompound action potentialDorsal columnsSpinal cordAction potentialsWhite matterSpinal cord dorsal columnAdult rat spinal cordAdult spinal cordRat spinal cordMin of reoxygenationAdult white matterAction potential conductionControl ratsFocal demyelinationAnoxic injurySupramaximal stimulationOnset of anoxiaAdult ratsDemyelinationPotential conductionCordX-irradiationRatsGreater recoveryOnset
1996
Action potential-like responses in B 104 cells with low Na+ channel densities
Gu X, Waxman S. Action potential-like responses in B 104 cells with low Na+ channel densities. Brain Research 1996, 735: 50-58. PMID: 8905169, DOI: 10.1016/0006-8993(96)00604-x.Peer-Reviewed Original ResearchConceptsAction potential-like responsesB104 cellsWhole-cell patch-clamp methodB104 neuroblastoma cellsPA/pFCurrent-clamp modeSteady-state inactivationAction potential generationPatch-clamp methodMicroM TTXNeuroblastoma cellsPrepulse potentialPotential generationResponse amplitudeCellsResponseStimuli
1994
Intracellular calcium mobilization and neurite outgrowth in mammalian neurons
Kocsis J, Rand M, Lankford K, Waxman S. Intracellular calcium mobilization and neurite outgrowth in mammalian neurons. Developmental Neurobiology 1994, 25: 252-264. PMID: 8195789, DOI: 10.1002/neu.480250306.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsCaffeineCalciumCalcium ChannelsCell CompartmentationCell DifferentiationCells, CulturedFemaleGanglia, SpinalGene Expression RegulationImage Processing, Computer-AssistedIntracellular FluidIon Channel GatingLasersMicroscopy, FluorescenceModels, BiologicalNeuritesNeuronsRatsRats, WistarTerpenesThapsigarginConceptsDepolarization-induced Ca2Calcium-induced calcium releaseDRG neuronsIntracellular Ca2Cultured adult rat dorsal root ganglion neuronsAdult rat dorsal root ganglion neuronsRat dorsal root ganglion neuronsNeurite outgrowthDorsal root ganglion neuronsIntact intracellular Ca2Intracellular calcium mobilizationIndicator dye fluo-3Nuclear Ca2Dye Fluo-3Endoplasmic reticulum Ca2Ganglion neuronsCalcium mobilizationDependent kinase IICalcium releaseFluo-3NeuronsMammalian neuronsReticulum Ca2Elevated Ca2Elicit neurite outgrowth
1991
Differential sensitivity to hypoxia of the peripheral versus central trajectory of primary afferent axons
Utzschneider D, Kocsis J, Waxman S. Differential sensitivity to hypoxia of the peripheral versus central trajectory of primary afferent axons. Brain Research 1991, 551: 136-141. PMID: 1913145, DOI: 10.1016/0006-8993(91)90924-k.Peer-Reviewed Original ResearchConceptsDorsal columnsDorsal rootsAfferent fibersCentral nervous system componentsPrimary afferent fibersSucrose gap chamberAction potential amplitudePrimary afferent axonsCompound action potentialDorsal spinal rootsNervous system componentsAxonal trunksPeripheral nervesSpinal cordSpinal rootsAfferent axonsCNS portionSchwann cellsAdult ratsPotential amplitudeAxon branchesAction potentialsHypoxiaMembrane potential changesMembrane depolarizationCompound action potential of nerve recorded by suction electrode: a theoretical and experimental analysis
Stys P, Ransom B, Waxman S. Compound action potential of nerve recorded by suction electrode: a theoretical and experimental analysis. Brain Research 1991, 546: 18-32. PMID: 1855148, DOI: 10.1016/0006-8993(91)91154-s.Peer-Reviewed Original Research
1990
Anoxic injury of mammalian central white matter: Decreased susceptibility in myelin‐deficient optic nerve
Waxman S, Davis P, Black J, Ransom B. Anoxic injury of mammalian central white matter: Decreased susceptibility in myelin‐deficient optic nerve. Annals Of Neurology 1990, 28: 335-340. PMID: 2241117, DOI: 10.1002/ana.410280306.Peer-Reviewed Original ResearchConceptsCompound action potentialOptic nerveCentral white matterMinutes of anoxiaAction potentialsMD ratsWhite matterMammalian central white matterSupramaximal compound action potentialCompound action potential amplitudeAction potential amplitudeNeonatal optic nerveRat optic nerveControl optic nervesDistinct action potentialsWhite matter tractsUnaffected male littermatesAnoxic injuryMale littermatesDays postnatalNervePotential amplitudeOligodendroglial proliferationEffects of anoxiaAdult pattern