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 ResearchMeSH KeywordsAction PotentialsAnimalsGanglia, SpinalHumansMiceNAV1.7 Voltage-Gated Sodium ChannelNAV1.8 Voltage-Gated Sodium ChannelNeuralgiaNeuronsRatsConceptsDorsal 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 generation
2023
Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function
Jami S, Deuis J, Klasfauseweh T, Cheng X, Kurdyukov S, Chung F, Okorokov A, Li S, Zhang J, Cristofori-Armstrong B, Israel M, Ju R, Robinson S, Zhao P, Ragnarsson L, Andersson Å, Tran P, Schendel V, McMahon K, Tran H, Chin Y, Zhu Y, Liu J, Crawford T, Purushothamvasan S, Habib A, Andersson D, Rash L, Wood J, Zhao J, Stehbens S, Mobli M, Leffler A, Jiang D, Cox J, Waxman S, Dib-Hajj S, Neely G, Durek T, Vetter I. Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function. Nature Communications 2023, 14: 2442. PMID: 37117223, PMCID: PMC10147923, DOI: 10.1038/s41467-023-37963-2.Peer-Reviewed Original ResearchMeSH KeywordsAustraliaNAV1.7 Voltage-Gated Sodium ChannelPainPeptidesToxins, BiologicalUrtica dioicaConceptsSensory neuronsVoltage-sensing domainNav channelsTransmembrane proteinAccessory proteinsVoltage-gated sodium channelsCritical regulatorPore domainChannel gatingExtracellular loopToxin-mediated effectsNeuronal excitabilityPeptide toxinsProteinSodium channelsPharmacological activitiesNav1.7 functionKnottin peptidesNeuronsImportant insightsToxinSubunitsRegulatorDomainExcelsa
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
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 ResearchMeSH KeywordsExonsFemaleGanglia, SpinalHEK293 CellsHumansMiddle AgedNAV1.7 Voltage-Gated Sodium ChannelPatch-Clamp TechniquesPolyneuropathiesSodium ChannelsConceptsSmall 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