2022
The fates of internalized NaV1.7 channels in sensory neurons: Retrograde cotransport with other ion channels, axon-specific recycling, and degradation
Higerd-Rusli G, Tyagi S, Liu S, Dib-Hajj F, Waxman S, Dib-Hajj S. The fates of internalized NaV1.7 channels in sensory neurons: Retrograde cotransport with other ion channels, axon-specific recycling, and degradation. Journal Of Biological Chemistry 2022, 299: 102816. PMID: 36539035, PMCID: PMC9843449, DOI: 10.1016/j.jbc.2022.102816.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAxonsHumansIon ChannelsMembrane ProteinsNAV1.7 Voltage-Gated Sodium ChannelSensory Receptor CellsConceptsMembrane proteinsIon channelsNeuronal functionDistinct neuronal compartmentsAxonal membrane proteinsRetrograde traffickingNeuronal polarityRecycling pathwayLate endosomesPlasma membraneSpecific proteinsAxonal traffickingNovel mechanismCell membraneSodium channel NaNeuronal compartmentsMultiple pathwaysLive neuronsVoltage-gated sodium channel NaProteinEndocytosisMembrane specializationsTraffickingMembraneChannel NaStem cell-derived sensory neurons modelling inherited erythromelalgia: normalization of excitability
Alsaloum M, Labau JIR, Liu S, Effraim P, Waxman SG. Stem cell-derived sensory neurons modelling inherited erythromelalgia: normalization of excitability. Brain 2022, 146: 359-371. PMID: 35088838, PMCID: PMC10060693, DOI: 10.1093/brain/awac031.Peer-Reviewed Original ResearchMeSH KeywordsErythromelalgiaGanglia, SpinalHumansMutationNAV1.7 Voltage-Gated Sodium ChannelPainSensory Receptor CellsConceptsSensory neuronsPluripotent stem cell-derived sensory neuronsDynamic clamp electrophysiologyMediators of painUnmet healthcare needsEffective therapeutic approachErythromelalgia mutationAmeliorate painNeuronal hyperexcitabilityPain disordersClinical studiesNeuronal excitabilityPreclinical studiesTherapeutic approachesEffective treatmentNaV1.7 currentsBaseline levelsClamp electrophysiologyHealthcare needsNav1.7 channelsPainErythromelalgiaHyperexcitabilityFunction mutationsNav1.7
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 modelsPaclitaxel increases axonal localization and vesicular trafficking of Nav1.7
Akin EJ, Alsaloum M, Higerd GP, Liu S, Zhao P, Dib-Hajj FB, Waxman SG, Dib-Hajj SD. Paclitaxel increases axonal localization and vesicular trafficking of Nav1.7. Brain 2021, 144: 1727-1737. PMID: 33734317, PMCID: PMC8320304, DOI: 10.1093/brain/awab113.Peer-Reviewed Original ResearchConceptsDorsal root ganglion neuronsChemotherapy-induced peripheral neuropathyGanglion neuronsSensory axonsNav1.7 channelsPTX treatmentSensory neuronsHuman sensory neuronsEffect of paclitaxelSodium channel Nav1.7Chemotherapy drug paclitaxelAxonal vesicular transportConcentrations of paclitaxelNav1.7 mRNAInflammatory mediatorsNav1.7 expressionPeripheral neuropathyInflammatory milieuPrimary afferentsInflammatory conditionsChannel expressionChannel Nav1.7Nav1.7Increased expressionAxonal localization
2019
Building sensory axons: Delivery and distribution of NaV1.7 channels and effects of inflammatory mediators
Akin EJ, Higerd-Rusli GP, Mis MA, Tanaka BS, Adi T, Liu S, Dib-Hajj FB, Waxman SG, Dib-Hajj SD. Building sensory axons: Delivery and distribution of NaV1.7 channels and effects of inflammatory mediators. Science Advances 2019, 5: eaax4755. PMID: 31681845, PMCID: PMC6810356, DOI: 10.1126/sciadv.aax4755.Peer-Reviewed Original ResearchConceptsMicrotubule-dependent vesicular transportSingle-molecule resolutionVesicular traffickingVesicular transportSurface deliveryPlasma membraneMembrane distributionFunctional studiesAxon terminiSodium channel NaLive visualizationSensory axonsVesiclesTraffickingNew insightsChannel NaContribution of NaDisease statesRab6ANav1.7 channelsDorsal root ganglion neuronsTerminusThreefold increaseGanglion neuronsMembrane
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 variants
2012
Neuropathy‐associated NaV1.7 variant I228M impairs integrity of dorsal root ganglion neuron axons
Persson A, Liu S, Faber CG, Merkies IS, Black JA, Waxman SG. Neuropathy‐associated NaV1.7 variant I228M impairs integrity of dorsal root ganglion neuron axons. Annals Of Neurology 2012, 73: 140-145. PMID: 23280954, DOI: 10.1002/ana.23725.Peer-Reviewed Original ResearchConceptsSmall fiber neuropathyIntraepidermal nerve fibersIdiopathic small fiber neuropathyNa-Ca exchangeDRG neuronsNeurite lengthSensory axonsLoss of IENFsReverse Na-Ca exchangeDorsal root ganglion neuronsPeripheral sensory axonsPeripheral nerve axonsSodium channel blockers carbamazepineSodium channel activityAxonal degenerationGanglion neuronsSpontaneous firingNerve fibersAxonal integrityNeuron axonsImpaired regenerationNerve axonsFunction variantsAxonsSodium channels