2021
Contributions of NaV1.8 and NaV1.9 to excitability in human induced pluripotent stem-cell derived somatosensory neurons
Alsaloum M, Labau JIR, Liu S, Estacion M, Zhao P, Dib-Hajj F, Waxman SG. Contributions of NaV1.8 and NaV1.9 to excitability in human induced pluripotent stem-cell derived somatosensory neurons. Scientific Reports 2021, 11: 24283. PMID: 34930944, PMCID: PMC8688473, DOI: 10.1038/s41598-021-03608-x.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAutopsyCell DifferentiationElectrophysiologyHumansImmunohistochemistryInduced Pluripotent Stem CellsMembrane PotentialsMutationNAV1.8 Voltage-Gated Sodium ChannelNAV1.9 Voltage-Gated Sodium ChannelNeuronsNeurosciencesPainPatch-Clamp TechniquesProtein IsoformsSensory Receptor CellsSomatosensory CortexConceptsNeuronal excitabilitySomatosensory neuronsPluripotent stem cell-derived sensory neuronsDynamic clamp electrophysiologyTreatment of painPromising novel modalityVoltage-gated sodium channelsSodium channel isoformsNeuronal membrane potentialGenetic knockout modelsNav1.9 currentsPharmacologic blockSensory neuronsNav1.8Cellular correlatesRepetitive firingClamp electrophysiologyExcitabilityNeuronal backgroundNovel modalityChannel isoformsSodium channelsNeuronsNav1.9Knockout models
2018
Resilience to Pain: A Peripheral Component Identified Using Induced Pluripotent Stem Cells and Dynamic Clamp
Mis MA, Yang Y, Tanaka BS, Gomis-Perez C, Liu S, Dib-Hajj F, Adi T, Garcia-Milian R, Schulman BR, Dib-Hajj SD, Waxman SG. Resilience to Pain: A Peripheral Component Identified Using Induced Pluripotent Stem Cells and Dynamic Clamp. Journal Of Neuroscience 2018, 39: 382-392. PMID: 30459225, PMCID: PMC6335750, DOI: 10.1523/jneurosci.2433-18.2018.Peer-Reviewed Original ResearchMeSH KeywordsAdultChildChronic PainErythromelalgiaExcitatory Postsynaptic PotentialsExomeFemaleGanglia, SpinalHumansImmunohistochemistryIndividualityInduced Pluripotent Stem CellsKCNQ Potassium ChannelsMaleMembrane PotentialsNAV1.7 Voltage-Gated Sodium ChannelPain MeasurementPatch-Clamp TechniquesResilience, PsychologicalSensory Receptor CellsConceptsWhole-exome sequencingPeripheral sensory neuronsSensory neuronsSpecific gene variantsGene variantsPluripotent stem cell-derived sensory neuronsInterindividual differencesDorsal root ganglion neuronsExome sequencingDifferent pain profilesDRG neuron excitabilityDynamic clampPeripheral nervous systemStem cellsPain ProfilePluripotent stem cellsChronic painPeripheral mechanismsGanglion neuronsNeuron excitabilityPainNervous systemHuman genetic modelsNeuronsDifferent gene variantsAtypical changes in DRG neuron excitability and complex pain phenotype associated with a Nav1.7 mutation that massively hyperpolarizes activation
Huang J, Mis MA, Tanaka B, Adi T, Estacion M, Liu S, Walker S, Dib-Hajj SD, Waxman SG. Atypical changes in DRG neuron excitability and complex pain phenotype associated with a Nav1.7 mutation that massively hyperpolarizes activation. Scientific Reports 2018, 8: 1811. PMID: 29379075, PMCID: PMC5788866, DOI: 10.1038/s41598-018-20221-7.Peer-Reviewed Original ResearchConceptsNav1.7 mutationClinical presentationDRG neuronsPain sensationDorsal root ganglion neuronsDRG neuron excitabilityFunction Nav1.7 mutationsLoss of excitabilityAbsence of painSodium channel Nav1.7Function mutationsComplex pain phenotypesEpisodic painSevere painCorneal anesthesiaGanglion neuronsNeuron excitabilityClinical lossPain phenotypesPainChannel Nav1.7Atypical changesNav1.7 channelsClinical levelNeurons
2014
Contribution of sodium channels to lamellipodial protrusion and Rac1 and ERK1/2 activation in ATP‐stimulated microglia
Persson A, Estacion M, Ahn H, Liu S, Stamboulian‐Platel S, Waxman SG, Black JA. Contribution of sodium channels to lamellipodial protrusion and Rac1 and ERK1/2 activation in ATP‐stimulated microglia. Glia 2014, 62: 2080-2095. PMID: 25043721, DOI: 10.1002/glia.22728.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsAnimals, NewbornBrainCell MovementCells, CulturedEnzyme ActivationEnzyme InhibitorsGene Expression RegulationMembrane PotentialsMiceMice, TransgenicMicrogliaMitogen-Activated Protein Kinase 3NAV1.6 Voltage-Gated Sodium ChannelPseudopodiaRac1 GTP-Binding ProteinRatsRats, Sprague-DawleySignal TransductionSodium Channel BlockersConceptsActin-rich membrane protrusionsStream signaling cascadesAccumulation of Rac1Modulation of Rac1Sodium channel activityChannel activitySodium channelsP38α/βCellular polarizationMembrane protrusionsSignal transductionLamellipodial protrusionCellular pathwaysSignaling cascadesCoordinated processCytoskeletal elementsMembrane adhesionRac1Dependent pathwayPhosphorylated ERK1/2Central nervous systemATPERK1/2ATP stimulationActivated state
2004
Changes in the expression of tetrodotoxin‐sensitive sodium channels within dorsal root ganglia neurons in inflammatory pain
Black JA, Liu S, Tanaka M, Cummins TR, Waxman SG. Changes in the expression of tetrodotoxin‐sensitive sodium channels within dorsal root ganglia neurons in inflammatory pain. Pain 2004, 108: 237-247. PMID: 15030943, DOI: 10.1016/j.pain.2003.12.035.Peer-Reviewed Original ResearchMeSH KeywordsAnesthetics, LocalAnimalsBlotting, WesternCarrageenanCells, CulturedDisease Models, AnimalFunctional LateralityGanglia, SpinalGene Expression RegulationImmunohistochemistryIn Situ HybridizationInflammationMaleMembrane PotentialsNeuronsPainPatch-Clamp TechniquesRatsRats, Sprague-DawleyRNA, MessengerSodium ChannelsTetrodotoxinConceptsTTX-R currentsDorsal root gangliaDRG neuronsInflammatory painSodium channelsCarrageenan injectionProstaglandin E2TTX-R sodium channelsTetrodotoxin-sensitive sodium channelsDorsal root ganglion neuronsMultiple voltage-gated sodium channelsWhole-cell patch-clamp methodTTX-S sodium channelsTTX-R channelsTTX-S currentsSmall DRG neuronsInjection of carrageenanTTX-S channelsChronic inflammation resultsTetrodotoxin-resistant channelsVoltage-gated sodium channelsPatch-clamp methodUpregulation of mRNAAffected pawAcute administration