2018
A novel gain-of-function Nav1.7 mutation in a carbamazepine-responsive patient with adult-onset painful peripheral neuropathy
Adi T, Estacion M, Schulman BR, Vernino S, Dib-Hajj S, Waxman S. A novel gain-of-function Nav1.7 mutation in a carbamazepine-responsive patient with adult-onset painful peripheral neuropathy. Molecular Pain 2018, 14: 1744806918815007. PMID: 30392441, PMCID: PMC6856981, DOI: 10.1177/1744806918815007.Peer-Reviewed Original ResearchConceptsPainful peripheral neuropathyDorsal root gangliaPeripheral neuropathyUse-dependent inhibitionDRG neuronsPain disordersM variantFunction Nav1.7 mutationsMulti-electrode array recordingsSympathetic ganglion neuronsCommon pain disordersVoltage-clamp recordingsVoltage-gated sodium channel NaRare MendelianNav1.7 mutationGanglion neuronsSodium channel NaTrigeminal ganglionRoot gangliaNeonatal ratsPatientsNeuropathyMutant channelsFunction variantsNeurons
2012
Hodgkin and Huxley and the basis for electrical signalling: a remarkable legacy still going strong
Vandenberg J, Waxman S. Hodgkin and Huxley and the basis for electrical signalling: a remarkable legacy still going strong. The Journal Of Physiology 2012, 590: 2569-2570. PMID: 22787169, PMCID: PMC3424715, DOI: 10.1113/jphysiol.2012.233411.Peer-Reviewed Original Research
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 membraneElectrogenesis
2000
Sodium channels and their genes: dynamic expression in the normal nervous system, dysregulation in disease states11Published on the World Wide Web on 15 August 2000.
Waxman S, Dib-Hajj S, Cummins T, Black J. Sodium channels and their genes: dynamic expression in the normal nervous system, dysregulation in disease states11Published on the World Wide Web on 15 August 2000. Brain Research 2000, 886: 5-14. PMID: 11119683, DOI: 10.1016/s0006-8993(00)02774-8.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsSodium channel gene expressionSodium channel geneChannel gene expressionChannel genesGene expressionPost-transcriptional levelNormal nervous systemSodium channel expressionSodium channelsChannel expressionMolecular plasticityGenesDynamic expressionCell membraneHypothalamic magnocellular neurosecretory neuronsDifferent repertoiresMultiple sclerosisNervous systemTherapeutic opportunitiesSodium channel subtypesExpressionElectrogenic propertiesRegulationChannel subtypesDysregulationDevelopment 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 eventsActivityWeeksCourseReceptors
1999
Characterization of a new sodium channel mutation at arginine 1448 associated with moderate paramyotonia congenita in humans
Bendahhou S, Cummins T, Kwiecinski H, Waxman S, Ptácek L. Characterization of a new sodium channel mutation at arginine 1448 associated with moderate paramyotonia congenita in humans. The Journal Of Physiology 1999, 518: 337-344. PMID: 10381583, PMCID: PMC2269438, DOI: 10.1111/j.1469-7793.1999.0337p.x.Peer-Reviewed Original ResearchConceptsChannel functionMutant channelsHuman embryonic kidney 293 cellsEmbryonic kidney 293 cellsSodium channel alpha subunitAmino acid changesSingle nucleotide substitutionKidney 293 cellsChannel alpha subunitSkeletal muscle voltage-gated sodium channelPosition 1448Sodium channel mutationsParamyotonia congenitaVoltage-gated sodium channelsSodium channel functionNucleotide substitutionsAlpha subunitSingle-strand conformation polymorphism analysisSegment S4Skeletal muscle disordersDomain IVAcid changesNew genetic mutationsDNA sequencingFast inactivationChanges 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 NGFThe role of voltage-gated Ca2+ channels in anoxic injury of spinal cord white matter
Imaizumi T, Kocsis J, Waxman S. The role of voltage-gated Ca2+ channels in anoxic injury of spinal cord white matter. Brain Research 1999, 817: 84-92. PMID: 9889329, DOI: 10.1016/s0006-8993(98)01214-1.Peer-Reviewed Original ResearchConceptsVoltage-gated Ca2Spinal cord axonsAnoxic injuryDorsal columnsR-type voltage-gated Ca2N-type calcium channelsSpinal cord white matterRat dorsal columnsDorsal column axonsR-type Ca2Rat spinal cordCord white matterT-type channelsInflux of Ca2Dose-dependent mannerLoss of conductionAxonal conductionSpinal cordChannel blockersCalcium channelsSurface stimulationWhite matterPerfusion solutionInjuryGlass microelectrodes
1998
SNS 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 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
Manipulation of the delayed rectifier Kv1.5 potassium channel in glial cells by antisense oligodeoxynucleotides
Roy M, Saal D, Perney T, Sontheimer H, Waxman S, Kaczmarek L. Manipulation of the delayed rectifier Kv1.5 potassium channel in glial cells by antisense oligodeoxynucleotides. Glia 1996, 18: 177-184. PMID: 8915650, DOI: 10.1002/(sici)1098-1136(199611)18:3<177::aid-glia2>3.0.co;2-x.Peer-Reviewed Original ResearchConceptsGlial cellsKv1.5 channel proteinSpinal cordKv1.5 proteinCultured spinal cordTEA-insensitive currentSpinal cord astrocytesRectifier current densityPotassium channel typesAntisense oligodeoxynucleotide treatmentKv1.5 potassium channelAdult ratsCerebellar slicesChannel proteinsAstrocytesOligodeoxynucleotide treatmentPotassium channelsRectifier currentEndfoot processesSuch treatmentCurrent activationAntisense oligodeoxynucleotidesCordCellsTreatmentMechanisms 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
Astrocyte 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
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
Depolarization-dependent actions of dihydropyridines on synaptic transmission in the in vitro rat hippocampus
O'Regan M, Kocsis J, Waxman S. Depolarization-dependent actions of dihydropyridines on synaptic transmission in the in vitro rat hippocampus. Brain Research 1990, 527: 181-191. PMID: 1701335, DOI: 10.1016/0006-8993(90)91136-5.Peer-Reviewed Original ResearchMeSH Keywords3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl esterAnimalsCaffeineDihydropyridinesEvoked PotentialsFemaleHippocampusIn Vitro TechniquesLightMembrane PotentialsNeuronsNifedipineNimodipinePerfusionPotassiumPyramidal TractsRatsRats, Inbred StrainsSynapsesSynaptic TransmissionConceptsBay K 8644Synaptic transmissionDepressant actionIntracellular recordingsModerate membrane depolarizationMembrane depolarizationHippocampal brain slicesNormal Krebs solutionField potential responsesDepolarization-dependent increaseField potential analysisCA1 neuronsPresynaptic locusHippocampal slicesKrebs solutionPostsynaptic componentsPostsynaptic responsesPyramidal cellsNeuronal excitabilityRat hippocampusBrain slicesDirect depolarizationSpike thresholdDHP effectField potentials