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
2003
Primary cortical motor neurons undergo apoptosis after axotomizing spinal cord injury
Hains B, Black J, Waxman S. Primary cortical motor neurons undergo apoptosis after axotomizing spinal cord injury. The Journal Of Comparative Neurology 2003, 462: 328-341. PMID: 12794736, DOI: 10.1002/cne.10733.Peer-Reviewed Original ResearchConceptsSpinal cord injuryCortical motor neuronsFluoro-GoldCorticospinal tractCord injuryMotor neuronsTerminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphateAdult male Sprague-Dawley ratsRetrograde tracer Fluoro-GoldMale Sprague-Dawley ratsApoptotic cell deathDorsal corticospinal tractPrimary motor cortexTracer Fluoro-GoldSprague-Dawley ratsVoluntary motor controlTUNEL-positive cellsCell deathEvidence of apoptosisSham surgeryDorsal funiculusMotor cortexPyramidal cellsLesion sitePositive cells
2002
HSV-1 Helper Virus 5dl1.2 Suppresses Sodium Currents in Amplicon-Transduced Neurons
White BH, Cummins TR, Wolf DH, Waxman SG, Russell DS, Kaczmarek LK. HSV-1 Helper Virus 5dl1.2 Suppresses Sodium Currents in Amplicon-Transduced Neurons. Journal Of Neurophysiology 2002, 87: 2149-2157. PMID: 11929932, DOI: 10.1152/jn.00498.2001.Peer-Reviewed Original ResearchConceptsSodium currentAnti-HSV antibodiesAverage spike frequencyWild-type HSV-1Helper virusViral-based strategiesDays of transductionCultured neuronsHSV-1Spike frequencyGene deliveryNeuronsMammalian neuronsAmplicon systemSimilar suppressionHSV-1 genesVirusTherapeutic purposesViral proteinsAmplicon preparationsCellsCoinfectionSuppressionPreparation resultsTitersNitric Oxide Blocks Fast, Slow, and Persistent Na+ Channels in C-Type DRG Neurons by S-Nitrosylation
Renganathan M, Cummins T, Waxman S. Nitric Oxide Blocks Fast, Slow, and Persistent Na+ Channels in C-Type DRG Neurons by S-Nitrosylation. Journal Of Neurophysiology 2002, 87: 761-775. PMID: 11826045, DOI: 10.1152/jn.00369.2001.Peer-Reviewed Original ResearchConceptsSteady-state voltage-dependent inactivationDorsal root ganglion neuronsNitric oxide blockIncubation of neuronsNO scavenger hemoglobinSlow sodium channel inactivationNitric oxide donorFast TTXMembrane-permeable analogSlow TTXVoltage-dependent inactivationDRG neuronsGanglion neuronsSodium channel inactivationCurrent inhibitionOxide donorScavenger hemoglobinPersistent TTXPAPA-NONOateS-nitrosoTTXNeuronsChannel inactivationSlow inactivationCGMP-dependent protein kinase
2001
Glycosylation Alters Steady-State Inactivation of Sodium Channel Nav1.9/NaN in Dorsal Root Ganglion Neurons and Is Developmentally Regulated
Tyrrell L, Renganathan M, Dib-Hajj S, Waxman S. Glycosylation Alters Steady-State Inactivation of Sodium Channel Nav1.9/NaN in Dorsal Root Ganglion Neurons and Is Developmentally Regulated. Journal Of Neuroscience 2001, 21: 9629-9637. PMID: 11739573, PMCID: PMC6763018, DOI: 10.1523/jneurosci.21-24-09629.2001.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsAnimals, NewbornAntibody SpecificityAxotomyCell MembraneCells, CulturedFemaleGanglia, SpinalGlycosylationImmunoblottingMembrane PotentialsN-Acetylneuraminic AcidNAV1.9 Voltage-Gated Sodium ChannelNeuraminidaseNeuronsNeuropeptidesPatch-Clamp TechniquesRatsRats, Sprague-DawleySciatic NerveSodiumSodium ChannelsSubcellular FractionsTetrodotoxinTrigeminal GanglionConceptsImmunoreactive proteinMembrane fractionAdult DRG neuronsTranscription-PCR analysisHigh molecular weight immunoreactive proteinTheoretical molecular weightWhole-cell patch-clamp analysisLong transcriptsGlycosylation statePatch-clamp analysisAdult tissuesLarge proteinsLimited glycosylationEnzymatic deglycosylationExtensive glycosylationState of glycosylationProteinAdult dorsal root gangliaGlycosylationNative neuronsDevelopmental changesInactivationMembrane preparationsDRG neuronsDorsal root gangliaDirect Interaction with Contactin Targets Voltage-gated Sodium Channel Nav1.9/NaN to the Cell Membrane*
Liu C, Dib-Hajj S, Black J, Greenwood J, Lian Z, Waxman S. Direct Interaction with Contactin Targets Voltage-gated Sodium Channel Nav1.9/NaN to the Cell Membrane*. Journal Of Biological Chemistry 2001, 276: 46553-46561. PMID: 11581273, DOI: 10.1074/jbc.m108699200.Peer-Reviewed Original ResearchConceptsDorsal root gangliaRoot gangliaSodium channelsSmall sensory neuronsVoltage-gated sodium channelsTrigeminal ganglionNerve endingsC-fibersSensory neuronsNeuron somataChinese hamster ovary cell lineDifferent physiological propertiesGangliaHamster ovary cell lineNeuronal membranesChinese hamster ovary cellsOvary cell lineProtein complexesSurface expressionHamster ovary cellsCell linesAxonsSurface localizationCell membraneOvary cellsβ1 adducin gene expression in DRG is developmentally regulated and is upregulated by glial-derived neurotrophic factor and nerve growth factor
Ghassemi F, Dib-Hajj S, Waxman S. β1 adducin gene expression in DRG is developmentally regulated and is upregulated by glial-derived neurotrophic factor and nerve growth factor. Brain Research 2001, 90: 118-124. PMID: 11406290, DOI: 10.1016/s0169-328x(01)00091-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalmodulin-Binding ProteinsCells, CulturedCytoskeletonGanglia, SpinalGene Expression ProfilingGene Expression Regulation, DevelopmentalGlial Cell Line-Derived Neurotrophic FactorNerve Growth FactorNerve Growth FactorsNerve Tissue ProteinsNeurons, AfferentNeuroprotective AgentsRatsRats, Sprague-DawleyReverse Transcriptase Polymerase Chain ReactionConceptsGlial-derived neurotrophic factorReal-time reverse transcription-polymerase chain reactionNeurotrophic factorTrigeminal ganglionDRG culturesRat DRGGrowth factorDorsal root ganglion culturesAdult rat DRGRat dorsal root ganglion culturesSuperior cervical ganglionReverse transcription-polymerase chain reactionExpression levelsNerve growth factorNon-neural tissuesDRG tissueCervical ganglionSciatic nervePolymerase chain reactionGanglion culturesAdducin geneLevel of expressionGangliaLow expression levelsGene expression
2000
Development of Glutamatergic Synaptic Activity in Cultured Spinal Neurons
Robert A, Howe J, Waxman S. Development of Glutamatergic Synaptic Activity in Cultured Spinal Neurons. Journal Of Neurophysiology 2000, 83: 659-670. PMID: 10669482, DOI: 10.1152/jn.2000.83.2.659.Peer-Reviewed Original ResearchMeSH Keywords2-Amino-5-phosphonovalerate6-Cyano-7-nitroquinoxaline-2,3-dioneAnimalsCells, CulturedExcitatory Amino Acid AntagonistsExcitatory Postsynaptic PotentialsFetusGlutamic AcidMagnesiumMembrane PotentialsNeuronsPatch-Clamp TechniquesQuinoxalinesRatsRats, Sprague-DawleyReceptors, AMPAReceptors, N-Methyl-D-AspartateSpinal CordSynapsesTetrodotoxinConceptsSpontaneous synaptic activityCultured spinal neuronsSynaptic activitySpinal neuronsGlutamatergic synapsesSynaptic currentsGlutamatergic synaptic activityIsoxazolepropionic acid (AMPA) receptorsSpontaneous synaptic currentsOlder neuronsSynaptic NMDARsExogenous glutamateNMDARAcid receptorsSynaptic regionNeuronsReceptor openingSignificant increaseTime courseSynapsesSequence of eventsActivityWeeksCourseReceptorsLocalization of the tetrodotoxin-resistant sodium channel NaN in nociceptors
Fjell J, Hjelmström P, Hormuzdiar W, Milenkovic M, Aglieco F, Tyrrell L, Dib-Hajj S, Waxman S, Black J. Localization of the tetrodotoxin-resistant sodium channel NaN in nociceptors. Neuroreport 2000, 11: 199-202. PMID: 10683857, DOI: 10.1097/00001756-200001170-00039.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAxonsCorneaFemaleGanglia, SpinalImage Processing, Computer-AssistedImmunohistochemistryMolecular Sequence DataMyelin SheathNAV1.9 Voltage-Gated Sodium ChannelNerve FibersNeurons, AfferentNeuropeptidesNociceptorsPresynaptic TerminalsRanvier's NodesRatsRats, Sprague-DawleySciatic NerveSodium ChannelsTetrodotoxinConceptsSciatic nerveSmall diameter primary sensory neuronsSodium currentTetrodotoxin-resistant sodium channelsTetrodotoxin-resistant sodium currentDorsal root ganglion neuronsSodium channelsPrimary sensory neuronsAxonal sodium currentsNodes of RanvierNociceptive transmissionChannel immunoreactivityGanglion neuronsUnmyelinated fibersAxon terminalsSensory neuronsNerveImmunoreactivityAxonsNeuronsSpecific peptidesNociceptorsIB4CorneaAntibodies
1999
Plasticity of sodium channel expression in DRG neurons in the chronic constriction injury model of neuropathic pain
Dib-Hajj S, Fjell J, Cummins TR, Zheng Z, Fried K, LaMotte R, Black JA, Waxman S. Plasticity of sodium channel expression in DRG neurons in the chronic constriction injury model of neuropathic pain. Pain 1999, 83: 591-600. PMID: 10568868, DOI: 10.1016/s0304-3959(99)00169-4.Peer-Reviewed Original ResearchConceptsTTX-R sodium channelsChronic constriction injury modelDRG neuronsSodium currentSodium channelsNeuropathic painInjury modelAxotomized dorsal root ganglion (DRG) neuronsSmall-diameter DRG neuronsTTX-R sodium currentsDorsal root ganglion neuronsTTX-S currentsSodium channel expressionGanglion neuronsSciatic nerveChannel expressionSodium channel transcriptsNeuronsNa currentPainChannel transcriptsSignificant changesLevels of transcriptsHyperalgesiaPrevious studiesChanges in expression of voltage‐gated potassium channels in dorsal root ganglion neurons following axotomy
Ishikawa K, Tanaka M, Black J, Waxman S. Changes in expression of voltage‐gated potassium channels in dorsal root ganglion neurons following axotomy. Muscle & Nerve 1999, 22: 502-507. PMID: 10204786, DOI: 10.1002/(sici)1097-4598(199904)22:4<502::aid-mus12>3.0.co;2-k.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxotomyGanglia, SpinalImmunohistochemistryIon Channel GatingMaleMembrane PotentialsNeuronsPotassium ChannelsRatsRats, Sprague-DawleyConceptsDorsal root ganglion neuronsDRG neuronsVoltage-gated potassium channelsAxonal injuryGanglion neuronsPotassium channelsChannel expressionNormal DRG neuronsChronic pain syndromeSodium channel expressionSpectrum of subtypesVoltage-gated sodium channelsSpecific potassium channelsPain syndromeDRG cellsAdult ratsNervous systemAxotomyKv expressionNeuronsImmunocytochemical methodsMolecular correlatesElectrical excitabilitySodium channelsImmunoreactivityDifferential role of GDNF and NGF in the maintenance of two TTX-resistant sodium channels in adult DRG neurons
Fjell J, Cummins T, Dib-Hajj S, Fried K, Black J, Waxman S. Differential role of GDNF and NGF in the maintenance of two TTX-resistant sodium channels in adult DRG neurons. Brain Research 1999, 67: 267-282. PMID: 10216225, DOI: 10.1016/s0169-328x(99)00070-4.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnimalsAxotomyCell SizeCell SurvivalDown-RegulationDrug ResistanceFemaleGanglia, SpinalGene ExpressionGlial Cell Line-Derived Neurotrophic FactorLectinsMembrane PotentialsNAV1.8 Voltage-Gated Sodium ChannelNAV1.9 Voltage-Gated Sodium ChannelNerve Growth FactorsNerve Tissue ProteinsNeurons, AfferentNeuropeptidesPatch-Clamp TechniquesRatsRats, Sprague-DawleyRNA, MessengerSciatic NerveSodium ChannelsTetrodotoxinUp-RegulationConceptsTTX-R sodium currentsSNS/PN3Small DRG neuronsTTX-R currentsDRG neuronsIB4- neuronsSodium currentElectrophysiological propertiesSmall dorsal root ganglion neuronsDorsal root ganglion neuronsAxotomized DRG neuronsTTX-S currentsWhole-cell patch-clamp studiesTTX-resistant sodium channelsSciatic nerve transectionAdult DRG neuronsDifferent electrophysiological propertiesNear-normal levelsPatch-clamp studiesNerve transectionGDNF treatmentNeurotrophins NGFGanglion neuronsIsolectin IB4Exogenous NGFIn Vivo NGF Deprivation Reduces SNS Expression and TTX-R Sodium Currents in IB4-Negative DRG Neurons
Fjell J, Cummins T, Fried K, Black J, Waxman S. In Vivo NGF Deprivation Reduces SNS Expression and TTX-R Sodium Currents in IB4-Negative DRG Neurons. Journal Of Neurophysiology 1999, 81: 803-810. PMID: 10036280, DOI: 10.1152/jn.1999.81.2.803.Peer-Reviewed Original ResearchConceptsTTX-R sodium currentsNerve growth factorPA/pFDRG neuronsHigh antibody titersSodium current densityNGF-deprived neuronsSodium currentAntibody titersAdult ratsSmall dorsal root ganglion neuronsTetrodotoxin-resistant sodium channelsDorsal root ganglion neuronsTTX-R currentsSodium channel expressionMRNA hybridization signalsPathological painThermal hypoalgesiaGanglion neuronsControl neuronsIsolectin IB4Channel expressionNGF deprivationMRNA expressionNeurons
1998
Slow Closed-State Inactivation: A Novel Mechanism Underlying Ramp Currents in Cells Expressing the hNE/PN1 Sodium Channel
Cummins T, Howe J, Waxman S. Slow Closed-State Inactivation: A Novel Mechanism Underlying Ramp Currents in Cells Expressing the hNE/PN1 Sodium Channel. Journal Of Neuroscience 1998, 18: 9607-9619. PMID: 9822722, PMCID: PMC6793269, DOI: 10.1523/jneurosci.18-23-09607.1998.Peer-Reviewed Original ResearchConceptsTTX-S currentsRamp currentsDRG neuronsClosed-state inactivationSensory neuronsChannel isoformsDistinct integrative propertiesSmall DRG neuronsSodium channelsTTX-sensitive currentsSlow ramp depolarizationSteady-state inactivationRamp depolarizationNeuronsSkeletal muscleState inactivationIntegrative propertiesInactivation propertiesOpen-state inactivationExcitable cellsNovel mechanismCellsDepolarizationInactivationPN1Endogenous NMDA-Receptor Activation Regulates Glutamate Release in Cultured Spinal Neurons
Robert A, Black J, Waxman S. Endogenous NMDA-Receptor Activation Regulates Glutamate Release in Cultured Spinal Neurons. Journal Of Neurophysiology 1998, 80: 196-208. PMID: 9658041, DOI: 10.1152/jn.1998.80.1.196.Peer-Reviewed Original ResearchMeSH Keywords2-Amino-5-phosphonovalerate6-Cyano-7-nitroquinoxaline-2,3-dioneAnimalsAnimals, NewbornBicucullineCells, CulturedExcitatory Amino Acid AntagonistsExcitatory Postsynaptic PotentialsGlutamic AcidNeuronsRatsRats, Sprague-DawleyReceptors, AMPAReceptors, N-Methyl-D-AspartateSpinal CordSynapsesTetrodotoxinTime FactorsConceptsAMPA excitatory postsynaptic currentsExcitatory postsynaptic currentsNMDA receptor activationCultured spinal neuronsNMDA receptorsSpinal neuronsPresynaptic terminalsNMDA receptor-mediated glutamatergic neurotransmissionSpontaneous excitatory postsynaptic currentsAspartate receptor activationNMDA receptor activityRelease of neurotransmittersNonsynaptic receptorsTTX applicationGlutamate releaseImmature neuronsGlutamatergic neurotransmissionPostsynaptic currentsSpinal cordReceptor activationReceptor activityQuantal sizeQuantal analysisCNS developmentElectrical activityEffects of Glucose Deprivation, Chemical Hypoxia, and Simulated Ischemia on Na+ Homeostasis in Rat Spinal Cord Astrocytes
Rose C, Waxman S, Ransom B. Effects of Glucose Deprivation, Chemical Hypoxia, and Simulated Ischemia on Na+ Homeostasis in Rat Spinal Cord Astrocytes. Journal Of Neuroscience 1998, 18: 3554-3562. PMID: 9570787, PMCID: PMC6793162, DOI: 10.1523/jneurosci.18-10-03554.1998.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornAntimetabolitesAstrocytesBenzofuransCell HypoxiaDeoxyglucoseEnergy MetabolismEnzyme InhibitorsEthers, CyclicExcitatory Amino Acid AgonistsFluorescent DyesFluorides, TopicalGlucoseGlycolysisHomeostasisIschemiaKainic AcidNeurotoxinsOuabainRatsRats, Sprague-DawleySodiumSodium AzideSodium FluorideSodium-Potassium-Exchanging ATPaseSpinal CordTetrodotoxinConceptsSpinal cord astrocytesChemical hypoxiaGlucose deprivationEnergy failureCultured spinal cord astrocytesGlutamatergic agonist kainateGlucose salineGlutamate reuptakeVivo ischemiaSpinal cordGlial functionMetabolic insultsSimulated ischemiaAgonist kainateIschemiaStandard salineAstrocytesSalineHypoxiaIntracellular ion concentrationsGlucose removalExtracellular spaceDeprivationL-lactateReperfusionNovel splice variants of the voltage-sensitive sodium channel alpha subunit
Oh Y, Waxman S. Novel splice variants of the voltage-sensitive sodium channel alpha subunit. Neuroreport 1998, 9: 1267-1272. PMID: 9631410, DOI: 10.1097/00001756-199805110-00002.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAmino Acid SequenceAnimalsAnimals, NewbornAstrocytesAstrocytomaBrainBucladesineCalcimycinCells, CulturedGenetic VariationMacromolecular SubstancesModels, MolecularMolecular Sequence DataPolymerase Chain ReactionProtein ConformationRatsRats, Sprague-DawleySodium ChannelsSpinal CordUp-RegulationConceptsChannel alpha subunitNeuroblastoma cellsSpinal cord astrocytesB104 neuroblastoma cellsCultured rat astrocytesChannel mRNA expressionNovel splice variantSplice variantsSodium channel alpha subunitAlpha-subunit mRNASpinal cordCerebral astrocytesUnique regulatory pathwaysAlpha subunitRat astrocytesAstrocytesMRNA expressionSubunit mRNAsMicroM A23187Dibutyryl cAMPPremature truncationCellsExpressionRegulatory pathwaysCordSNS Na+ channel expression increases in dorsal root ganglion neurons in the carrageenan inflammatory pain model
Tanaka M, Cummins T, Ishikawa K, Dib-Hajj S, Black J, Waxman S. SNS Na+ channel expression increases in dorsal root ganglion neurons in the carrageenan inflammatory pain model. Neuroreport 1998, 9: 967-972. PMID: 9601651, DOI: 10.1097/00001756-199804200-00003.Peer-Reviewed Original ResearchConceptsSmall DRG neuronsDorsal root ganglion neuronsInjection of carrageenanDRG neuronsInflamed limbGanglion neuronsSodium currentTTX-R sodium currentsTetrodotoxin-resistant sodium currentInflammatory pain modelDevelopment of hyperexcitabilitySodium channel expressionPatch-clamp recordingsInflammatory painPain modelChronic painCarrageenan injectionNociceptive cellsContralateral sideNaive ratsChannel expressionProjection fieldsMRNA expressionNeuronsSodium channels
1997
Pharmacological Characterization of Na+ Influx via Voltage-Gated Na+ Channels in Spinal Cord Astrocytes
Rose C, Ransom B, Waxman S. Pharmacological Characterization of Na+ Influx via Voltage-Gated Na+ Channels in Spinal Cord Astrocytes. Journal Of Neurophysiology 1997, 78: 3249-3258. PMID: 9405543, DOI: 10.1152/jn.1997.78.6.3249.Peer-Reviewed Original ResearchConceptsSpinal cordChannel inactivationCultured spinal cordSpinal cord astrocytesEffect of veratridineSodium-binding benzofuranMicroM tetrodotoxinPharmacological characterizationAgonist kainatePharmacological inhibitionTetrodotoxinAstrocytesVeratridineCordMembrane depolarizationKainateImportant functional roleInfluxFunctional roleInhibitionCellsProminent pathwayATPase activityInactivationBaselineRegulation of Na+ channel β1 and β2 subunit mRNA levels in cultured rat astrocytes
Oh Y, Lee Y, Waxman S. Regulation of Na+ channel β1 and β2 subunit mRNA levels in cultured rat astrocytes. Neuroscience Letters 1997, 234: 107-110. PMID: 9364509, DOI: 10.1016/s0304-3940(97)00694-0.Peer-Reviewed Original ResearchConceptsReverse transcription-polymerase chain reactionMRNA levelsSpinal cordCompetitive reverse transcription-polymerase chain reactionQuantitative competitive reverse transcription-polymerase chain reactionSpinal cord astrocytesRat optic nerveDibutyryl cAMPBeta 2 mRNACultured rat astrocytesTranscription-polymerase chain reactionBeta 1 mRNASubunit mRNA levelsNeuroblastoma cell linesOptic nerveChannel β1Cultured astrocytesRat astrocytesCalcium ionophoreAstrocytesBeta 1Chain reactionCell linesCordMRNA