2019
NaV1.6 regulates excitability of mechanosensitive sensory neurons
Israel MR, Tanaka BS, Castro J, Thongyoo P, Robinson SD, Zhao P, Deuis JR, Craik DJ, Durek T, Brierley SM, Waxman SG, Dib‐Hajj S, Vetter I. NaV1.6 regulates excitability of mechanosensitive sensory neurons. The Journal Of Physiology 2019, 597: 3751-3768. PMID: 31087362, DOI: 10.1113/jp278148.Peer-Reviewed Original ResearchConceptsPeripheral sensory neuronsPeripheral nervous systemDorsal root ganglion neuronsSensory neuronsVoltage-gated sodium channelsGanglion neuronsSodium channelsLarge-diameter dorsal root ganglion neuronsTonic action potential firingWhole-cell patch-clamp recordingsMultiple voltage-gated sodium channelsIntra-plantar injectionMechanosensitive sensory neuronsVivo behavioral assessmentsAction potential firingChannel activationPatch-clamp recordingsPotential therapeutic targetMechanical stimuliΒ-scorpion toxinSodium channel isoformsPain pathwaysThermal allodyniaPain generationSensory afferents
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
2016
Familial gain-of-function Nav1.9 mutation in a painful channelopathy
Han C, Yang Y, Morsche R, Drenth JP, Politei JM, Waxman SG, Dib-Hajj SD. Familial gain-of-function Nav1.9 mutation in a painful channelopathy. Journal Of Neurology Neurosurgery & Psychiatry 2016, 88: 233. PMID: 27503742, DOI: 10.1136/jnnp-2016-313804.Peer-Reviewed Original ResearchConceptsPain disordersPainful small fiber neuropathyDorsal root ganglion neuronsSmall fiber neuropathyPotential therapeutic targetVoltage-clamp recordingsFunction mutationsPain symptomsGastrointestinal disturbancesGanglion neuronsClinical examinationHyperpolarising shiftFunctional assessmentTherapeutic targetDistal extremitiesPhenotypic spectrumElectrophysiological recordingsPatientsBlood relativesFirst arginine residuePainAcceleration of activationSegment 4ChannelopathiesDisorders
2012
An AnkyrinG-Binding Motif Is Necessary and Sufficient for Targeting Nav1.6 Sodium Channels to Axon Initial Segments and Nodes of Ranvier
Gasser A, Ho TS, Cheng X, Chang KJ, Waxman SG, Rasband MN, Dib-Hajj SD. An AnkyrinG-Binding Motif Is Necessary and Sufficient for Targeting Nav1.6 Sodium Channels to Axon Initial Segments and Nodes of Ranvier. Journal Of Neuroscience 2012, 32: 7232-7243. PMID: 22623668, PMCID: PMC3413458, DOI: 10.1523/jneurosci.5434-11.2012.Peer-Reviewed Original ResearchConceptsReporter proteinAxon initial segmentKinase phosphorylation siteSodium channelsIntracellular loop 2Nodes of RanvierFull-length channelGlutamic acid residuesPhosphorylation sitesMechanism of channelVoltage-gated sodium channelsAcid residuesLoop 2Functional mouseNav1.6 sodium channelsMotifProteinVivo analysisAnkyrinGSomatodendritic compartmentCultured neuronsInitial segmentVivoAction potentialsCells
2009
A sodium channel gene SCN9A polymorphism that increases nociceptor excitability
Estacion M, Harty TP, Choi J, Tyrrell L, Dib‐Hajj S, Waxman SG. A sodium channel gene SCN9A polymorphism that increases nociceptor excitability. Annals Of Neurology 2009, 66: 862-866. PMID: 20033988, DOI: 10.1002/ana.21895.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArginineBiophysical PhenomenaCell Line, TransformedElectric StimulationGanglia, SpinalGreen Fluorescent ProteinsHumansMembrane PotentialsMiceNAV1.7 Voltage-Gated Sodium ChannelNociceptorsPatch-Clamp TechniquesPolymorphism, Single NucleotideSensory Receptor CellsSensory ThresholdsSodium ChannelsTransfectionTryptophanConceptsNonsynonymous single nucleotide polymorphismsNociceptive primary sensory neuronsDorsal root ganglion neuronsPrimary sensory neuronsCurrent-clamp analysisSingle nucleotide polymorphismsSCN9A geneDRG neuronsNociceptor excitabilityGanglion neuronsUnaffected family membersControl chromosomesSensory neuronsSmall depolarizationSodium channelsMembrane potentialNeuronsAffected probandPolymorphismFamily membersDepolarizationChromosomesGenesErythromelalgiaPain
2006
Sporadic onset of erythermalgia: A gain‐of‐function mutation in Nav1.7
Han C, Rush AM, Dib‐Hajj S, Li S, Xu Z, Wang Y, Tyrrell L, Wang X, Yang Y, Waxman SG. Sporadic onset of erythermalgia: A gain‐of‐function mutation in Nav1.7. Annals Of Neurology 2006, 59: 553-558. PMID: 16392115, DOI: 10.1002/ana.20776.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAmino Acid SequenceCell LineChinaDNA Mutational AnalysisDose-Response Relationship, RadiationElectric StimulationErythromelalgiaExonsFamily HealthHumansLeucineMaleMembrane PotentialsModels, MolecularMutationNAV1.7 Voltage-Gated Sodium ChannelPatch-Clamp TechniquesPhenylalanineSodium ChannelsTransfectionConceptsSporadic casesPeripheral sensory neuronsWhole-cell patch-clamp analysisAsymptomatic family membersPatch-clamp analysisAutosomal dominant disorderMild thermal stimuliSporadic onsetSensory neuronsErythermalgiaAsymptomatic fatherSmall depolarizationSodium channelsFounder mutationDominant disorderClamp analysisChannel activationThermal stimuliPatientsFunction mutationsFamily membersMultigeneration familySingle amino acid substitutionAmino acid substitutionsChinese family
2005
Contactin regulates the current density and axonal expression of tetrodotoxin‐resistant but not tetrodotoxin‐sensitive sodium channels in DRG neurons
Rush AM, Craner MJ, Kageyama T, Dib‐Hajj S, Waxman SG, Ranscht B. Contactin regulates the current density and axonal expression of tetrodotoxin‐resistant but not tetrodotoxin‐sensitive sodium channels in DRG neurons. European Journal Of Neuroscience 2005, 22: 39-49. PMID: 16029194, DOI: 10.1111/j.1460-9568.2005.04186.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsCell Adhesion Molecules, NeuronalCell MembraneCells, CulturedContactinsDown-RegulationGanglia, SpinalMembrane PotentialsMiceMice, Inbred C57BLMice, KnockoutNAV1.8 Voltage-Gated Sodium ChannelNAV1.9 Voltage-Gated Sodium ChannelNerve Fibers, UnmyelinatedNeurons, AfferentNeuropeptidesNociceptorsPatch-Clamp TechniquesPlant LectinsSodium Channel BlockersSodium ChannelsTetrodotoxinConceptsTTX-S channelsDRG neuronsSodium channelsSmall-diameter dorsal root ganglion neuronsSmall-diameter DRG neuronsWhole-cell patch-clamp recordingsTetrodotoxin-sensitive sodium channelsDorsal root ganglion neuronsChannel isoformsNociceptive DRG neuronsTTX-sensitive sodium channelsSodium channel Nav1.2Patch-clamp recordingsSodium channel isoformsPositive neuronsGanglion neuronsSciatic nerveCell surface expressionIsolectin B4Axonal expressionUnmyelinated axonsMammalian neuronal cellsLitter matesNav1.9Neuronal cellsElectrophysiological properties of two axonal sodium channels, Nav1.2 and Nav1.6, expressed in mouse spinal sensory neurones
Rush AM, Dib‐Hajj S, Waxman SG. Electrophysiological properties of two axonal sodium channels, Nav1.2 and Nav1.6, expressed in mouse spinal sensory neurones. The Journal Of Physiology 2005, 564: 803-815. PMID: 15760941, PMCID: PMC1464456, DOI: 10.1113/jphysiol.2005.083089.Peer-Reviewed Original Research
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 ganglia
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 subtypesDysregulation
1999
Differential 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
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
TTX-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