2025
Enhanced trafficking of an inherited erythromelalgia NaV1.7 mutant channel at a physiological temperature
Mis M, Tyagi S, Akin E, Ghovanloo M, Zhao P, Dib-Hajj F, Randall A, Waxman S, Dib-Hajj S. Enhanced trafficking of an inherited erythromelalgia NaV1.7 mutant channel at a physiological temperature. Neurobiology Of Pain 2025, 18: 100188. DOI: 10.1016/j.ynpai.2025.100188.Peer-Reviewed Original ResearchMutant channelsIB4- neuronsInherited ErythromelalgiaEnhanced traffickingActivity of Nav1.7Expressed sodium channelsHuman pain disordersCurrent-clamp recordingsDRG sensory neuronsVoltage-clamp recordingsAttacks of burning painGain-of-function mutationsIncreased membrane insertionHyperpolarizing shiftNeuronal hyperexcitabilityPain disordersCurrent-clampNav1.7 channelsWT channelsSensory neuronsSodium channelsIncreased firingTemporary reliefNeuronsSkin temperature
2024
Nav1.8 in small dorsal root ganglion neurons contributes to vincristine-induced mechanical allodynia
Nascimento de Lima A, Zhang H, Chen L, Effraim P, Gomis-Perez C, Cheng X, Huang J, Waxman S, Dib-Hajj S. Nav1.8 in small dorsal root ganglion neurons contributes to vincristine-induced mechanical allodynia. Brain 2024, 147: 3157-3170. PMID: 38447953, DOI: 10.1093/brain/awae071.Peer-Reviewed Original ResearchDorsal root ganglion neuronsDorsal root ganglionVincristine-induced mechanical allodyniaVincristine-induced peripheral neuropathyMechanical allodyniaVincristine treatmentNav1.8 channelsSmall dorsal root ganglion neuronsDevelopment of mechanical allodyniaTTX-R current densityVoltage-gated sodium channel Nav1.6Vincristine-treated animalsCurrent-clamp recordingsSodium channel Nav1.8Voltage-clamp recordingsReducing current thresholdSodium channel Nav1.6Investigate pathophysiological mechanismsTTX-RHyperpolarizing shiftRoot ganglionAllodyniaGanglion neuronsVincristine administrationPeripheral neuropathy
2023
Conserved but not critical: Trafficking and function of NaV1.7 are independent of highly conserved polybasic motifs
Tyagi S, Sarveswaran N, Higerd-Rusli G, Liu S, Dib-Hajj F, Waxman S, Dib-Hajj S. Conserved but not critical: Trafficking and function of NaV1.7 are independent of highly conserved polybasic motifs. Frontiers In Molecular Neuroscience 2023, 16: 1161028. PMID: 37008789, PMCID: PMC10060856, DOI: 10.3389/fnmol.2023.1161028.Peer-Reviewed Original ResearchSensory axonsPeripheral voltage-gated sodium channelsMajor unmet clinical needFunction of Nav1.7Non-addictive treatmentsUnmet clinical needVoltage-clamp recordingsVoltage-gated sodium channelsPain therapyChronic painPrimary afferentsNoxious stimuliTherapeutic modalitiesAction potentialsAxonal transportClinical needVesicular packagingSodium channelsHuman painPainAxonal traffickingAxonal surfaceAxonal membraneAxonsAttractive target
2021
KCNQ variants and pain modulation: a missense variant in Kv7.3 contributes to pain resilience
Yuan JH, Estacion M, Mis MA, Tanaka BS, Schulman BR, Chen L, Liu S, Dib-Hajj FB, Dib-Hajj SD, Waxman SG. KCNQ variants and pain modulation: a missense variant in Kv7.3 contributes to pain resilience. Brain Communications 2021, 3: fcab212-. PMID: 34557669, PMCID: PMC8454204, DOI: 10.1093/braincomms/fcab212.Peer-Reviewed Original ResearchPluripotent stem cell-derived sensory neuronsNav1.7 mutationSensory neuronsPain ProfilePain phenotypesPain resilienceDorsal root ganglion neuronsDaily pain diaryPeripheral sensory neuronsMissense variantsVoltage-clamp recordingsSodium channel Nav1.7Different pain experiencesPotential genetic factorsWhole-exome sequencingLarger M-currentsErythromelalgia patientsNeuropathic painPain episodesModerate painPain diaryPain modulationSevere painInter-individual variabilityGanglion neurons
2020
Differential effect of lacosamide on Nav1.7 variants from responsive and non-responsive patients with small fibre neuropathy
Labau J, Estacion M, Tanaka BS, de Greef B, Hoeijmakers J, Geerts M, Gerrits MM, Smeets H, Faber CG, Merkies I, Lauria G, Dib-Hajj SD, Waxman SG. Differential effect of lacosamide on Nav1.7 variants from responsive and non-responsive patients with small fibre neuropathy. Brain 2020, 143: 771-782. PMID: 32011655, PMCID: PMC7089662, DOI: 10.1093/brain/awaa016.Peer-Reviewed Original ResearchConceptsSmall fiber neuropathyEffects of lacosamideNon-responsive patientsSubset of patientsCommon pain disordersRecent clinical studiesUse-dependent inhibitionUse-dependent mannerVoltage-clamp recordingsPotent sodium channel inhibitorSlow inactivationSodium channel inhibitorsNeuronal hyperexcitabilityResponsive patientsPain disordersNav1.7 mutationClinical studiesAchievable concentrationsPatientsLacosamideNeuropathyChannel inhibitorsSodium channelsPainFunction mutations
2019
A Novel Gain-of-Function Nav1.9 Mutation in a Child With Episodic Pain
Huang J, Estacion M, Zhao P, Dib-Hajj FB, Schulman B, Abicht A, Kurth I, Brockmann K, Waxman SG, Dib-Hajj SD. A Novel Gain-of-Function Nav1.9 Mutation in a Child With Episodic Pain. Frontiers In Neuroscience 2019, 13: 918. PMID: 31551682, PMCID: PMC6733892, DOI: 10.3389/fnins.2019.00918.Peer-Reviewed Original ResearchDorsal root gangliaDRG neuronsEpisodic painVoltage-gated sodium channel Nav1.9Episodic abdominal painLarger window currentSmall DRG neuronsTrigeminal ganglion neuronsCurrent-clamp recordingsAction potential firingHuman pain disordersVoltage-clamp recordingsChronic constipationAbdominal painMyenteric neuronsPain disordersGanglion neuronsPain phenotypesRoot gangliaCommon painNav1.9PainAction potentialsWindow currentPhenotypic spectrumModulators of Kv3 Potassium Channels Rescue the Auditory Function of Fragile X Mice
El-Hassar L, Song L, Tan WJT, Large CH, Alvaro G, Santos-Sacchi J, Kaczmarek LK. Modulators of Kv3 Potassium Channels Rescue the Auditory Function of Fragile X Mice. Journal Of Neuroscience 2019, 39: 4797-4813. PMID: 30936239, PMCID: PMC6561694, DOI: 10.1523/jneurosci.0839-18.2019.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAuditory PathwaysAuditory PerceptionBrain StemCochlear NucleusElectrophysiological PhenomenaEvoked Potentials, Auditory, Brain StemFemaleFragile X Mental Retardation ProteinFragile X SyndromeHydantoinsIn Vitro TechniquesMaleMiceMice, KnockoutPatch-Clamp TechniquesPyridinesShaw Potassium ChannelsConceptsAuditory brainstem responseWild-type animalsRepetitive firingABR wave ICurrent-clamp recordingsAuditory brainstem nucleiVoltage-clamp recordingsHigh-frequency firingSingle action potentialFragile X syndromeTrapezoid bodyBrainstem nucleiBrainstem responseMedial nucleusAuditory brainstemAuditory nerveWave IWave IVAction potentialsSensory stimuliKv3.1 channelsCentral processingMental retardation proteinHigh sound levelsMice
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 4ChannelopathiesDisordersNav1.7-A1632G Mutation from a Family with Inherited Erythromelalgia: Enhanced Firing of Dorsal Root Ganglia Neurons Evoked by Thermal Stimuli
Yang Y, Huang J, Mis MA, Estacion M, Macala L, Shah P, Schulman BR, Horton DB, Dib-Hajj SD, Waxman SG. Nav1.7-A1632G Mutation from a Family with Inherited Erythromelalgia: Enhanced Firing of Dorsal Root Ganglia Neurons Evoked by Thermal Stimuli. Journal Of Neuroscience 2016, 36: 7511-7522. PMID: 27413160, PMCID: PMC6705539, DOI: 10.1523/jneurosci.0462-16.2016.Peer-Reviewed Original ResearchConceptsRat DRG neuronsDorsal root ganglion neuronsDRG neuronsCurrent-clamp recordingsSodium channel Nav1.7Pain syndromeNav1.7 mutationGanglion neuronsThermal stimuliIEM patientsChannel Nav1.7Whole-cell current-clamp recordingsNav1.7 channelsFunction Nav1.7 mutationsSevere pain syndromeVoltage-gated sodium channel Nav1.7Voltage-clamp recordingsMutant Nav1.7 channelsMean firing frequencyMultielectrode array recordingsMutant channelsG mutationMultigeneration familySpontaneous firingSympathetic neuronsA Gain-of-Function Mutation in Nav1.6 in a Case of Trigeminal Neuralgia
Tanaka BS, Zhao P, Dib-Hajj FB, Morisset V, Tate S, Waxman SG, Dib-Hajj SD. A Gain-of-Function Mutation in Nav1.6 in a Case of Trigeminal Neuralgia. Molecular Medicine 2016, 22: 338-348. PMID: 27496104, PMCID: PMC5023517, DOI: 10.2119/molmed.2016.00131.Peer-Reviewed Original ResearchUnilateral facial painTrigeminal neuralgiaCentral nervous systemFacial painPain disordersTrigeminal nervePeripheral voltage-gated sodium channelsPhase 2 clinical studyWhole-cell voltage-clamp recordingsPeripheral nervous system neuronsDiagnosis of TNFunction mutationsIdiopathic trigeminal neuralgiaTrigeminal ganglion neuronsCurrent-clamp studiesResurgent sodium currentsHuman pain disordersHigh-frequency firingVoltage-clamp recordingsDe novo missense mutationsVoltage-gated sodium channelsMagnetic resonance imagingHigh-firing neuronsNovo missense mutationVascular compression
2015
Intracellular calcium affects prestin’s voltage operating point indirectly via turgor-induced membrane tension
Song L, Santos-Sacchi J. Intracellular calcium affects prestin’s voltage operating point indirectly via turgor-induced membrane tension. AIP Conference Proceedings 2015, 1703: 030009. DOI: 10.1063/1.4939324.Peer-Reviewed Original ResearchAstrocyte‐expressed FABP7 regulates dendritic morphology and excitatory synaptic function of cortical neurons
Ebrahimi M, Yamamoto Y, Sharifi K, Kida H, Kagawa Y, Yasumoto Y, Islam A, Miyazaki H, Shimamoto C, Maekawa M, Mitsushima D, Yoshikawa T, Owada Y. Astrocyte‐expressed FABP7 regulates dendritic morphology and excitatory synaptic function of cortical neurons. Glia 2015, 64: 48-62. PMID: 26296243, DOI: 10.1002/glia.22902.Peer-Reviewed Original ResearchConceptsFabp7 KO miceMedial prefrontal cortexMiniature excitatory postsynaptic currentsAberrant dendritic morphologyKO miceCortical neuronsDendritic morphologyNeuropsychiatric disordersWhole-cell voltage-clamp recordingsPrimary cortical neuronal culturesDendritic arbor growthNeuronal dendritic morphologyExcitatory synaptic functionCortical pyramidal neuronsExcitatory synapse numberCortical neuronal culturesExcitatory postsynaptic currentsAstrocyte-conditioned mediumPrimary cortical neuronsWild-type miceExcitatory synapse formationVoltage-clamp recordingsNovel therapeutic interventionsHuman neuropsychiatric disordersFatty acids
2013
Cocaine-Induced Changes of Synaptic Transmission in the Striatum are Modulated by Adenosine A2A Receptors and Involve the Tyrosine Phosphatase STEP
Chiodi V, Mallozzi C, Ferrante A, Chen JF, Lombroso PJ, Di Stasi AM, Popoli P, Domenici MR. Cocaine-Induced Changes of Synaptic Transmission in the Striatum are Modulated by Adenosine A2A Receptors and Involve the Tyrosine Phosphatase STEP. Neuropsychopharmacology 2013, 39: 569-578. PMID: 23989619, PMCID: PMC3895235, DOI: 10.1038/npp.2013.229.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCerebral CortexCocaineCorpus StriatumDopamine Uptake InhibitorsEnzyme InhibitorsGene Expression RegulationHumansIn Vitro TechniquesInhibitory Postsynaptic PotentialsMaleMiceMice, Inbred C57BLMice, KnockoutNeural PathwaysNeuronsProtein Tyrosine Phosphatases, Non-ReceptorReceptor, Adenosine A2ASynaptic TransmissionSynaptosomesVanadatesConceptsEffects of cocaineSynaptic transmissionAdenosine A2A receptorsStriatal-enriched protein tyrosine phosphatasePharmacological actionsA2A receptorsWhole-cell voltage-clamp recordingsA2AR antagonist ZM241385Excitatory post-synaptic currentsCocaine-induced reductionMedium spiny neuronsCocaine-induced changesVoltage-clamp recordingsPost-synaptic currentsA2AR knockout miceCorticostriatal slicesStriatal slicesPsychomotor effectsSpiny neuronsSynaptic mechanismsAntagonist ZM241385Synaptic depressionClamp recordingsBrain areasStriatumSmall-Fiber Neuropathy Nav1.8 Mutation Shifts Activation to Hyperpolarized Potentials and Increases Excitability of Dorsal Root Ganglion Neurons
Huang J, Yang Y, Zhao P, Gerrits MM, Hoeijmakers JG, Bekelaar K, Merkies IS, Faber CG, Dib-Hajj SD, Waxman SG. Small-Fiber Neuropathy Nav1.8 Mutation Shifts Activation to Hyperpolarized Potentials and Increases Excitability of Dorsal Root Ganglion Neurons. Journal Of Neuroscience 2013, 33: 14087-14097. PMID: 23986244, PMCID: PMC6618513, DOI: 10.1523/jneurosci.2710-13.2013.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAmino Acid SequenceAnimalsCells, CulturedGanglia, SpinalHumansIon Channel GatingMaleMembrane PotentialsMiceMice, TransgenicMiddle AgedMolecular Sequence DataMutation, MissenseNAV1.8 Voltage-Gated Sodium ChannelNeuronsPeripheral Nervous System DiseasesRatsRats, Sprague-DawleyConceptsDorsal root ganglion neuronsSmall DRG neuronsDRG neuronsGanglion neuronsAction potentialsIdiopathic small fiber neuropathySmall-diameter DRG neuronsWhole-cell voltage-clamp recordingsSmall-caliber nerve fibersVoltage-gated sodium channel Nav1.7Peripheral sensory neuronsCurrent-clamp studiesLimited treatment optionsSmall fiber neuropathySodium channel Nav1.8Voltage-clamp recordingsSodium channel Nav1.7Autonomic dysfunctionIncreases excitabilityTreatment optionsUnknown etiologyFunctional variantsNerve fibersSensory neuronsRamp depolarization
2010
The Slack Sodium-Activated Potassium Channel Provides a Major Outward Current in Olfactory Neurons of Kv1.3−/− Super-Smeller Mice
Lu S, Das P, Fadool DA, Kaczmarek LK. The Slack Sodium-Activated Potassium Channel Provides a Major Outward Current in Olfactory Neurons of Kv1.3−/− Super-Smeller Mice. Journal Of Neurophysiology 2010, 103: 3311-3319. PMID: 20393063, PMCID: PMC2888249, DOI: 10.1152/jn.00607.2009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBiophysicsCardiovascular AgentsCells, CulturedElectric StimulationGene Expression RegulationIn Vitro TechniquesKv1.3 Potassium ChannelMembrane PotentialsMiceMice, Inbred C57BLMice, KnockoutNerve Tissue ProteinsNeuronsOlfactory BulbPatch-Clamp TechniquesPotassium ChannelsPotassium Channels, Sodium-ActivatedPyrimidinesRNA InterferenceSodium Channel BlockersTetrodotoxinTransfectionConceptsMitral cellsOlfactory bulbOutward currentsOlfactory neuronsWildtype animalsPotassium channelsMajor outward currentVoltage-clamp recordingsVoltage-dependent potassium channelsNet outward currentIntracellular sodiumOB slicesPotassium channel genesCompensatory increaseFiring patternsWestern blottingRNA interference approachPrimary culturesEnhanced expressionDetection of odorsSame treatmentChannel genesMiceNeuronsOlfactory phenotypes
2001
Lateral hypothalamus: Early developmental expression and response to hypocretin (orexin)
Van Den Pol A, Patrylo P, Ghosh P, Gao X. Lateral hypothalamus: Early developmental expression and response to hypocretin (orexin). The Journal Of Comparative Neurology 2001, 433: 349-363. PMID: 11298360, DOI: 10.1002/cne.1144.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsAnimals, NewbornBrainCalciumCarrier ProteinsCells, CulturedElectrophysiologyEmbryo, MammalianHypothalamic Area, LateralImmunohistochemistryIn Vitro TechniquesIntracellular Signaling Peptides and ProteinsNeuronsNeuropeptidesOrexin ReceptorsOrexinsRatsRats, Sprague-DawleyReceptors, G-Protein-CoupledReceptors, NeuropeptideRNA, MessengerConceptsLateral hypothalamic areaSynaptic activityLH neuronsNeuronal activitySleep regulationWhole-cell patch-clamp recordingsRobust increaseAdult central nervous systemEndocrine controlPostnatal day 1Day of birthCentral nervous systemPatch-clamp recordingsVoltage-clamp recordingsEmbryonic day 19Hypocretin-1Excitatory influenceHypothalamic areaHypocretin-2Spinal cordMature brainFood intakeHypocretin systemLH cellsReceptor mRNA
2000
Evidence for coassembly of mutant GABACρ1 with GABAAγ2S, glycine α1 and glycine α2 receptor subunits in vitro
Pan Z, Zhang D, Zhang X, Lipton S. Evidence for coassembly of mutant GABACρ1 with GABAAγ2S, glycine α1 and glycine α2 receptor subunits in vitro. European Journal Of Neuroscience 2000, 12: 3137-3145. PMID: 10998097, DOI: 10.1046/j.1460-9568.2000.00198.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDose-Response Relationship, DrugElectrophysiologyGABA Antagonistsgamma-Aminobutyric AcidGene ExpressionIn Vitro TechniquesMutagenesisNeural InhibitionOocytesPicrotoxinProtein Structure, TertiaryRatsReceptors, GABAReceptors, GABA-AReceptors, GABA-BReceptors, GlycineRetinaXenopus laevisConceptsGlycine alpha1Rho1 subunitAlpha2 subunitHeteromeric receptorsGABA dose-response curveBlockade of GABAVoltage-clamp recordingsGamma-aminobutyric acidXenopus laevis oocyte expression systemTwo-electrode voltage-clamp recordingsDose-response curveResponse propertiesPicrotoxinin sensitivityOocyte expression systemGamma2 subunitGABAReceptor subunitsPharmacological propertiesReceptorsUnique gatingFunctional evidenceGABAAAlpha1Gamma2HomomericRedox modulation of recombinant human GABAA receptors
Pan Z, Zhang X, Lipton S. Redox modulation of recombinant human GABAA receptors. Neuroscience 2000, 98: 333-338. PMID: 10854765, DOI: 10.1016/s0306-4522(00)00114-7.Peer-Reviewed Original ResearchConceptsGABA receptorsRat retinal ganglion cellsRecombinant human GABAA receptorsRetinal ganglion cellsVoltage-clamp recordingsEffect of dithiothreitolLow GABA concentrationsTwo-electrode voltage-clamp recordingsRedox modulationHuman GABAA receptorsGanglion cellsXenopus oocyte expression systemGABAA receptorsModulatory effectsReceptor currentsOocyte expression systemReceptor responsesGABA concentrationPotentiationGABAReceptorsSubunit compositionHomomeric GABAAgent 5M3 domain
1998
Periodicity of Thalamic Spindle Waves Is Abolished by ZD7288,a Blocker of I h
Lüthi A, Bal T, McCormick D. Periodicity of Thalamic Spindle Waves Is Abolished by ZD7288,a Blocker of I h. Journal Of Neurophysiology 1998, 79: 3284-3289. PMID: 9636128, DOI: 10.1152/jn.1998.79.6.3284.Peer-Reviewed Original ResearchConceptsSpindle wavesHyperpolarization-activated cation current IhCurrent-clamp recordingsIntracellular recording techniquesBlock of IhVoltage-clamp recordingsRebound burstsThalamic activityRefractory periodPacemaker currentLocal applicationZD7288AfterdepolarizationsCurrent IhRecording techniquesRepetitive hyperpolarizationNetwork activityHyperpolarizationSlow rhythmicityFurther supportIH
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