2023
Sodium currents in naïve mouse dorsal root ganglion neurons: No major differences between sexes
Ghovanloo M, Tyagi S, Zhao P, Effraim P, Dib-Hajj S, Waxman S. Sodium currents in naïve mouse dorsal root ganglion neurons: No major differences between sexes. Channels 2023, 18: 2289256. PMID: 38055732, PMCID: PMC10761158, DOI: 10.1080/19336950.2023.2289256.Peer-Reviewed Original ResearchConceptsSexual dimorphismRodent dorsal root ganglion neuronsBiophysical propertiesDorsal root ganglion neuronsExpression patternsSex-dependent regulationVoltage-gated sodiumFunctional analysisGanglion neuronsRodent sensory neuronsMouse dorsal root ganglion neuronsNaïve WT miceNumber of cellsMixed populationDimorphismUniform experimental conditionsSex-dependent differencesSensory neuronsNative DRG neuronsPain pathwaysDRG neuronsWT miceClinical studiesNav currentsAdult males
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
2012
The NaV1.7 sodium channel: from molecule to man
Dib-Hajj SD, Yang Y, Black JA, Waxman SG. The NaV1.7 sodium channel: from molecule to man. Nature Reviews Neuroscience 2012, 14: 49-62. PMID: 23232607, DOI: 10.1038/nrn3404.Peer-Reviewed Original ResearchConceptsDorsal hornPain disordersNerve endingsNociceptive dorsal root ganglion (DRG) neuronsPainful small fiber neuropathyDorsal root ganglion neuronsVoltage-gated sodium channel Nav1.7Small fiber neuropathyTreatment of painFree nerve endingsSecond-order neuronsSmall molecule blockersSodium channel Nav1.7Function mutationsOlfactory sensory neuronsProbability of neuronsNav1.7 sodium channelSuperficial laminaeGanglion neuronsRisk factorsSympathetic neuronsSlow depolarizationSpinal cordCardiac deficitsSensory neurons
2002
Nitric 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 gangliaContribution 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 membraneElectrogenesisFibroblast Growth Factor Homologous Factor 1B Binds to the C Terminus of the Tetrodotoxin-resistant Sodium Channel rNav1.9a (NaN)*
Liu C, Dib-Hajj S, Waxman S. Fibroblast Growth Factor Homologous Factor 1B Binds to the C Terminus of the Tetrodotoxin-resistant Sodium Channel rNav1.9a (NaN)*. Journal Of Biological Chemistry 2001, 276: 18925-18933. PMID: 11376006, DOI: 10.1074/jbc.m101606200.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAmino Acid SequenceAnimalsBlotting, WesternCell LineConserved SequenceCytoplasmDNA, ComplementaryDrug ResistanceFibroblast Growth FactorsGene LibraryGlutathione TransferaseGrowth SubstancesHumansMiceModels, BiologicalMolecular Sequence DataNAV1.9 Voltage-Gated Sodium ChannelNeuropeptidesPlasmidsProtein BindingProtein Structure, TertiaryRatsReverse Transcriptase Polymerase Chain ReactionRNASequence Analysis, DNASequence Homology, Amino AcidSodium ChannelsTetrodotoxinTissue DistributionTwo-Hybrid System TechniquesConceptsC-terminusTerminal polypeptideTwo-hybrid screenMammalian cell linesC-terminal regionN-terminal 5Fibroblast growth factor family membersFibroblast growth factor (FGF) familySodium channelsAmino acid residuesFactor family membersGrowth factor family membersCytoplasmic domainFirst growth factorGrowth factor familyFactor familyIntracellular segmentAcid residuesCell membraneFunctional significanceChannel complexDirect interactionCell linesTerminusPolypeptide
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 studiesDifferential 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 NGF
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-lactateReperfusion
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 activityInactivationBaselineTTX-Sensitive and -Resistant Na+ Currents, and mRNA for the TTX-Resistant rH1 Channel, Are Expressed in B104 Neuroblastoma Cells
Gu X, Dib-Hajj S, Rizzo M, Waxman S. TTX-Sensitive and -Resistant Na+ Currents, and mRNA for the TTX-Resistant rH1 Channel, Are Expressed in B104 Neuroblastoma Cells. Journal Of Neurophysiology 1997, 77: 236-246. PMID: 9120565, DOI: 10.1152/jn.1997.77.1.236.Peer-Reviewed Original ResearchConceptsB104 neuroblastoma cellsTTX-resistant channelsB104 cellsNeuroblastoma cellsWhole-cell patch-clamp methodAbsence of TTXTTX-resistant currentTTX-sensitive currentsPresence of TTXPA/pFTranscription-polymerase chain reactionLong QT syndromeCell linesSteady-state inactivationNeuroblastoma cell linesAlpha-subunit mRNAPatch-clamp methodTTX-sensitiveHalf-maximal inhibitionInactivation time constantsChannel mRNATTXMembrane excitabilitySubunit mRNAsRT-PCR
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 amplitudeCellsResponseStimuliMechanisms of Paresthesiae, Dysesthesiae, and Hyperesthesiae: Role of Na+ Channel Heterogeneity
Rizzo M, Kocsis J, Waxman S. Mechanisms of Paresthesiae, Dysesthesiae, and Hyperesthesiae: Role of Na+ Channel Heterogeneity. European Neurology 1996, 36: 3-12. PMID: 8719643, DOI: 10.1159/000117192.Peer-Reviewed Original ResearchConceptsAxonal injuryCutaneous afferentsDorsal root ganglion neuronsAction potential activityNormal sensory functionEctopic impulsesDRG neuronsClinical syndromeGanglion neuronsSensory functionMembrane excitabilityInjuryNerve impulsesDysesthesiaeChannel physiologyMolecular changesParesthesiaeAfferentsPreliminary evidenceNeuronsEctopicMolecular mechanismsSensory anatomyPotential activityPopulation
1994
Anoxic injury of rat optic nerve: ultrastructural evidence for coupling between Na+ influx and Ca2+-mediated injury in myelinated CNS axons
Waxman S, Black J, Ransom B, Stys P. Anoxic injury of rat optic nerve: ultrastructural evidence for coupling between Na+ influx and Ca2+-mediated injury in myelinated CNS axons. Brain Research 1994, 644: 197-204. PMID: 8050031, DOI: 10.1016/0006-8993(94)91680-2.Peer-Reviewed Original ResearchConceptsOptic nerveOptic nerve axonsRat optic nerveNerve axonsBrain slice chamberCompound action potentialLoss of cristaeMicroM tetrodotoxinAnoxic injuryNormoxic controlsNerveAstrocyte processesPerinodal astrocyte processesWhite matterMyelinated axonsAstrocytic processesCNS axonsTetrodotoxinAction potentialsSlice chamberAxonsLoss of microtubulesCytoskeletal damageInjuryNormoxic conditionsAstrocyte 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