2020
Cumulative hydropathic topology of a voltage‐gated sodium channel at atomic resolution
Xenakis M, Kapetis D, Yang Y, Heijman J, Waxman S, Lauria G, Faber C, Smeets H, Westra R, Lindsey P. Cumulative hydropathic topology of a voltage‐gated sodium channel at atomic resolution. Proteins Structure Function And Bioinformatics 2020, 88: 1319-1328. PMID: 32447794, DOI: 10.1002/prot.25951.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceArcobacterBacterial ProteinsBinding SitesHydrophobic and Hydrophilic InteractionsIon Channel GatingModels, MolecularProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein Interaction Domains and MotifsSodiumThermodynamicsVoltage-Gated Sodium ChannelsConceptsVoltage-gated sodium channelsBacterial channelsPhysiological cellular activitySodium channelsCellular activitiesCell membraneBiological poresPore stabilityAtomic resolutionBiophysical significanceMembrane surfaceHydropathicityGenesProteinMutationsWide spectrumMembraneFunctional architectureAccumulationComputational frameworkSodium ionsPores
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
Nav1.7 is phosphorylated by Fyn tyrosine kinase which modulates channel expression and gating in a cell type-dependent manner
Li Y, Zhu T, Yang H, Dib-Hajj S, Waxman S, Yu Y, Xu TL, Cheng X. Nav1.7 is phosphorylated by Fyn tyrosine kinase which modulates channel expression and gating in a cell type-dependent manner. Molecular Pain 2018, 14: 1744806918782229. PMID: 29790812, PMCID: PMC6024516, DOI: 10.1177/1744806918782229.Peer-Reviewed Original ResearchConceptsND7/23 cellsDRG neuron excitabilityModulation of Nav1.7New pain therapeuticsVoltage-gated sodium channel Nav1.7Fyn kinaseWhole-cell recordingsSodium channel Nav1.7Elevated protein expressionCell type-specific modulationHuman embryonic kidney 293 cellsTyrosine kinasePain disordersEmbryonic kidney 293 cellsPain therapeuticsNeuron excitabilityPain perceptionMutant channelsChannel Nav1.7Kidney 293 cellsNav1.7HEK-293 cellsNav1.7 channelsCell type-dependent mannerType-dependent manner
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
2007
Channel, neuronal and clinical function in sodium channelopathies: from genotype to phenotype
Waxman SG. Channel, neuronal and clinical function in sodium channelopathies: from genotype to phenotype. Nature Neuroscience 2007, 10: 405-409. PMID: 17387329, DOI: 10.1038/nn1857.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChannelopathiesGenotypeHumansIon Channel GatingModels, BiologicalMutationNeuronsPhenotypeSodium ChannelsConceptsSodium channel functionClinical manifestationsClinical statusNeuronal functionChannel functionPositive clinical manifestationsSodium channelsIon channel mutationsNegative clinical manifestationsNeuronal hyperexcitabilityNeuronal hypoexcitabilityNeuronal activityClinical functionNervous systemSodium channelopathiesChannelopathiesChannel mutationsManifestationsCell backgroundPhysiological propertiesStatusHyperexcitabilityHypoexcitabilitySeizuresParalysis
2002
Primary motor neurons fail to up‐regulate voltage‐gated sodium channel Nav1.3/brain type III following axotomy resulting from spinal cord injury
Hains B, Black J, Waxman S. Primary motor neurons fail to up‐regulate voltage‐gated sodium channel Nav1.3/brain type III following axotomy resulting from spinal cord injury. Journal Of Neuroscience Research 2002, 70: 546-552. PMID: 12404508, DOI: 10.1002/jnr.10402.Peer-Reviewed Original ResearchConceptsSpinal cord injuryUpper motor neuronsPrimary motor cortexDorsal root gangliaMotor neuronsCord injuryMotor cortexRat primary motor cortexDorsal column transectionIpsilateral DRG neuronsCortical motor neuronsSciatic nerve transectionTraumatic head injuryFacial motor neuronsSodium channel expressionPrimary motor neuronsVoltage-gated sodium channelsPeripheral axotomyDRG neuronsNerve transectionLayer VControl brainsHead injuryRoot gangliaSpinal cordNitric 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
Direct 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 cells
2000
A double mutation in families with periodic paralysis defines new aspects of sodium channel slow inactivation
Bendahhou S, Cummins T, Hahn A, Langlois S, Waxman S, Ptácek L. A double mutation in families with periodic paralysis defines new aspects of sodium channel slow inactivation. Journal Of Clinical Investigation 2000, 106: 431-438. PMID: 10930446, PMCID: PMC314328, DOI: 10.1172/jci9654.Peer-Reviewed Original ResearchConceptsChannel slow inactivationPeriodic paralysisSlow inactivationSodium channel slow inactivationMalignant hyperthermia susceptibilitySkeletal muscle disordersHuman skeletal muscleParalytic attacksMuscle disordersHyperkalemic periodic paralysisSkeletal muscleParalysisDisease-causing mutationsNovel mutationsHyperKPPChannel defectsMolecular determinantsAlpha subunitMutant channelsMutationsDouble mutationInactivationPatientsTransmembrane segments S5
1999
Activation and Inactivation of the Voltage-Gated Sodium Channel: Role of Segment S5 Revealed by a Novel Hyperkalaemic Periodic Paralysis Mutation
Bendahhou S, Cummins T, Tawil R, Waxman S, Ptácek L. Activation and Inactivation of the Voltage-Gated Sodium Channel: Role of Segment S5 Revealed by a Novel Hyperkalaemic Periodic Paralysis Mutation. Journal Of Neuroscience 1999, 19: 4762-4771. PMID: 10366610, PMCID: PMC6782655, DOI: 10.1523/jneurosci.19-12-04762.1999.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedDNA Mutational AnalysisDNA PrimersGene ExpressionHumansHyperkalemiaIon Channel GatingKidneyKineticsMaleMiddle AgedMolecular Sequence DataNAV1.4 Voltage-Gated Sodium ChannelParalyses, Familial PeriodicPatch-Clamp TechniquesPoint MutationProtein Structure, TertiarySequence Homology, Amino AcidSodium ChannelsTransfectionConceptsSegments S5Point mutationsS5 segmentVoltage-Gated Sodium ChannelSodium channelsTransmembrane segments S5Cytoplasmic interfaceWild-type channelsParalysis phenotypeHomologous domainsVoltage-sensitive sodium channelsPotassium-aggravated myotoniaNew point mutationPhenylalanine substitutionSkeletal muscle disordersHyperkalaemic periodic paralysisFast inactivationSecond domainMutationsGenesChannel deactivationInactivationChannel activationSlow inactivationT704M mutationChanges 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 channelsImmunoreactivityThe 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
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 mechanismCellsDepolarizationInactivationPN1SNS 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 activityInactivationBaseline
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 oligodeoxynucleotidesCordCellsTreatmentVoltage-gated Na+ channels in glia: properties and possible functions
Sontheimer H, Black J, Waxman S. Voltage-gated Na+ channels in glia: properties and possible functions. Trends In Neurosciences 1996, 19: 325-331. PMID: 8843601, DOI: 10.1016/0166-2236(96)10039-4.Peer-Reviewed Original Research
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