2024
Interplay of Nav1.8 and Nav1.7 channels drives neuronal hyperexcitability in neuropathic pain
Vasylyev D, Zhao P, Schulman B, Waxman S. Interplay of Nav1.8 and Nav1.7 channels drives neuronal hyperexcitability in neuropathic pain. The Journal Of General Physiology 2024, 156: e202413596. PMID: 39378238, PMCID: PMC11465073, DOI: 10.1085/jgp.202413596.Peer-Reviewed Original ResearchConceptsDorsal root ganglionGain-of-function Nav1.7 mutationsDorsal root ganglion neuronsSodium channel Nav1.7Inherited erythromelalgiaNav1.7 mutationsNeuropathic painNeuronal hyperexcitabilityOpen-probabilityVoltage-gated sodium channel Nav1.7Hyperexcitability of DRG neuronsModel of neuropathic painSubthreshold membrane potential oscillationsResting membrane potentialMembrane potential oscillationsReduced firing probabilityIncreased rheobaseNav1.8 channelsDRG neuronsHuman genetic modelsNav1.8Root ganglionNav1.7 channelsNav1.7AP generationFunctionally-selective inhibition of threshold sodium currents and excitability in dorsal root ganglion neurons by cannabinol
Ghovanloo M, Effraim P, Tyagi S, Zhao P, Dib-Hajj S, Waxman S. Functionally-selective inhibition of threshold sodium currents and excitability in dorsal root ganglion neurons by cannabinol. Communications Biology 2024, 7: 120. PMID: 38263462, PMCID: PMC10805714, DOI: 10.1038/s42003-024-05781-x.Peer-Reviewed Original ResearchConceptsDorsal root ganglionDorsal root ganglion neuronal excitabilityDorsal root ganglion neuronsNeuronal excitabilityCurrent-clamp analysisSteady-state inactivationVoltage-dependent sodiumSlow inactivated stateAutomated patch clamp platformMultielectrode array recordingsNav currentsNeuropathic painSodium currentRoot ganglionGanglion neuronsSlow inactivationInactivated stateCurrent inhibitorsIon channelsNeuronsInhibitory effectCannabinolArray recordingsEndocannabinoidCannabinoid
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 malesHigh-throughput combined voltage-clamp/current-clamp analysis of freshly isolated neurons
Ghovanloo M, Tyagi S, Zhao P, Kiziltug E, Estacion M, Dib-Hajj S, Waxman S. High-throughput combined voltage-clamp/current-clamp analysis of freshly isolated neurons. Cell Reports Methods 2023, 3: 100385. PMID: 36814833, PMCID: PMC9939380, DOI: 10.1016/j.crmeth.2022.100385.Peer-Reviewed Original ResearchConceptsDorsal root ganglion neuronsCurrent-clamp recordingsCurrent-clamp analysisVoltage-gated sodium channelsPatch-clamp techniqueExcitable cellsGanglion neuronsElectrophysiological recordingsNeuronal cellsNeuronsGold standard methodologySodium channelsCellular levelRobotic instrumentsCellsDrug screeningSame cellsIntact tissueRecordings
2022
Fibroblast growth factor homologous factor 2 attenuates excitability of DRG neurons
Effraim PR, Estacion M, Zhao P, Sosniak D, Waxman SG, Dib-Hajj SD. Fibroblast growth factor homologous factor 2 attenuates excitability of DRG neurons. Journal Of Neurophysiology 2022, 128: 1258-1266. PMID: 36222860, PMCID: PMC9909838, DOI: 10.1152/jn.00361.2022.Peer-Reviewed Original ResearchConceptsDRG neuron excitabilityDRG neuronal excitabilityNeuronal excitabilityFibroblast growth factor homologous factorsNerve injuryDRG neuronsInflammatory mediatorsNeuron excitabilityDorsal root ganglion neuronsFunction of Nav1.7Peripheral nerve axotomyMultiple neurological disordersVoltage-gated sodium channelsDRG excitabilityFibroblast growth factor homologous factor 2Inflammatory painNerve axotomyGanglion neuronsIsoform-dependent mannerNeurological disordersBasal conditionsExcitabilityGating propertiesNeuron firingInjuryInhibition of sodium conductance by cannabigerol contributes to a reduction of dorsal root ganglion neuron excitability
Ghovanloo M, Estacion M, Higerd‐Rusli G, Zhao P, Dib‐Hajj S, Waxman SG. Inhibition of sodium conductance by cannabigerol contributes to a reduction of dorsal root ganglion neuron excitability. British Journal Of Pharmacology 2022, 179: 4010-4030. PMID: 35297036, DOI: 10.1111/bph.15833.Peer-Reviewed Original ResearchConceptsEffect of cannabigerolDRG neuronsDorsal root ganglion neuron excitabilityVoltage-gated sodium currentDorsal root ganglion neuronsLower CBG concentrationPrimary dorsal root ganglion neuronsAnalgesic drug developmentNon-psychotropic phytocannabinoidMultielectrode array recordingsAction potential modellingInhibition of NaDRG excitabilityGanglion neuronsNeuron excitabilityAnalgesic propertiesCNS neuronsNeuronal hypoexcitabilityCBG concentrationsChannel inhibitorsSodium currentNeuronsFunctional selectivityDrug developmentUnderlying mechanism
2014
Dynamic-clamp analysis of wild-type human Nav1.7 and erythromelalgia mutant channel L858H
Vasylyev DV, Han C, Zhao P, Dib-Hajj S, Waxman SG. Dynamic-clamp analysis of wild-type human Nav1.7 and erythromelalgia mutant channel L858H. Journal Of Neurophysiology 2014, 111: 1429-1443. PMID: 24401712, DOI: 10.1152/jn.00763.2013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiophysicsCells, CulturedElectric StimulationErythromelalgiaGanglia, SpinalHEK293 CellsHumansMembrane PotentialsMiceMice, KnockoutModels, BiologicalMutationNAV1.7 Voltage-Gated Sodium ChannelNeural ConductionNeuronsPatch-Clamp TechniquesSodium Channel BlockersTetrodotoxinTransfectionConceptsDRG neuronsMutant Nav1.7 channelsNav1.7 channelsDorsal root ganglion neuronsSodium influxPrimary nociceptive neuronsSmall DRG neuronsNet sodium influxSodium channel Nav1.7Current thresholdMechanistic linkAction potential generationNeuropathic painNociceptive neuronsNociceptor functionGanglion neuronsNociceptor hyperexcitabilityPain phenotypesChannel expressionChannel Nav1.7Subthreshold depolarizationHuman Nav1.7Electrophysiological recordingsDynamic-Clamp AnalysisIdentification of gain
2013
Sodium Channels Contribute to Degeneration of Dorsal Root Ganglion Neurites Induced by Mitochondrial Dysfunction in an In Vitro Model of Axonal Injury
Persson AK, Kim I, Zhao P, Estacion M, Black JA, Waxman SG. Sodium Channels Contribute to Degeneration of Dorsal Root Ganglion Neurites Induced by Mitochondrial Dysfunction in an In Vitro Model of Axonal Injury. Journal Of Neuroscience 2013, 33: 19250-19261. PMID: 24305821, PMCID: PMC6618782, DOI: 10.1523/jneurosci.2148-13.2013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsAxotomyCell DeathCells, CulturedGanglia, SpinalHumansHydrogen PeroxideImmunohistochemistryMiceMice, TransgenicMicrotubulesMitochondrial DiseasesNerve DegenerationNeuritesOxidantsRotenoneSodium Channel BlockersSodium ChannelsSodium-Calcium ExchangerSodium-Potassium-Exchanging ATPaseTetrodotoxinThioureaUncoupling AgentsConceptsAxonal degenerationNeurite degenerationSodium channelsKB-R7943Mouse peripheral sensory neuronsRotenone-induced mitochondrial dysfunctionOxidative stressMitochondrial dysfunctionPeripheral sensory neuronsDorsal root gangliaPeripheral nervous systemDegeneration of neuritesMitochondrial functionVoltage-gated sodium channelsMultiple neurodegenerative disordersSodium-calcium exchangerImpaired mitochondrial functionInjurious cascadeAxonal injuryActivity blockadeRoot gangliaAxonal neuropathySensory neuronsNCX activityDysfunctional intracellularSmall-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
2012
Nav1.7-related small fiber neuropathy
Han C, Hoeijmakers JG, Ahn H, Zhao P, Shah P, Lauria G, Gerrits MM, te Morsche R, Dib-Hajj SD, Drenth JP, Faber CG, Merkies IS, Waxman SG. Nav1.7-related small fiber neuropathy. Neurology 2012, 78: 1635-1643. PMID: 22539570, DOI: 10.1212/wnl.0b013e3182574f12.Peer-Reviewed Original ResearchConceptsSmall fiber neuropathyDorsal root gangliaDRG neuronsIdiopathic small fiber neuropathySmall-diameter peripheral axonsDRG neuron hyperexcitabilityIdentifiable underlying causeNerve conduction studiesQuantitative sensory testingSympathetic ganglion neuronsSFN symptomsNeuron hyperexcitabilityConduction studiesGanglion neuronsRoot gangliaSkin biopsiesDifferential diagnosisPeripheral axonsSensory testingVoltage-clamp analysisApparent causePatientsNoninactivating componentUnderlying causeSuprathreshold stimuli
2011
Nav1.7 is the Predominant Sodium Channel in Rodent Olfactory Sensory Neurons
Ahn HS, Black JA, Zhao P, Tyrrell L, Waxman SG, Dib-Hajj SD. Nav1.7 is the Predominant Sodium Channel in Rodent Olfactory Sensory Neurons. Molecular Pain 2011, 7: 1744-8069-7-32. PMID: 21569247, PMCID: PMC3101130, DOI: 10.1186/1744-8069-7-32.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGanglia, SpinalGene Expression RegulationIn Situ HybridizationIon Channel GatingMaleMiceMice, Inbred C57BLNAV1.6 Voltage-Gated Sodium ChannelNAV1.7 Voltage-Gated Sodium ChannelOlfactory MucosaOlfactory Receptor NeuronsPolymerase Chain ReactionRatsRats, Sprague-DawleyRNA, MessengerSodium ChannelsConceptsDorsal root gangliaOlfactory sensory neuronsSodium channelsSensory neuronsNervous systemSodium channel transcriptsVoltage-gated sodium channel Nav1.7Peripheral nervous systemCentral nervous systemCompound heterozygous lossSodium channel Nav1.7Channel transcriptsPeripheral olfactory sensory neuronsCongenital insensitivityRoot gangliaSympathetic neuronsOSN axonsOlfactory bulbPostsynaptic cellOlfactory epitheliumChannel Nav1.7Nav1.7Nav1.6 channelsNull miceAnosmia