2022
Stem 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 ResearchConceptsSensory 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 models
2018
Atypical 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
2016
A painful neuropathy-associated Nav1.7 mutant leads to time-dependent degeneration of small-diameter axons associated with intracellular Ca2+ dysregulation and decrease in ATP levels
Rolyan H, Liu S, Hoeijmakers JG, Faber CG, Merkies IS, Lauria G, Black JA, Waxman SG. A painful neuropathy-associated Nav1.7 mutant leads to time-dependent degeneration of small-diameter axons associated with intracellular Ca2+ dysregulation and decrease in ATP levels. Molecular Pain 2016, 12: 1744806916674472. PMID: 27821467, PMCID: PMC5102167, DOI: 10.1177/1744806916674472.Peer-Reviewed Original ResearchConceptsSmall fiber neuropathySmall-diameter axonsTime-dependent degenerationDorsal root ganglion neuronsNerve fiber injuryNervous system disordersPrevious clinical reportsIntracellular calcium levelsMutant Nav1.7 channelsATP levelsAδ nerve fibersHigh altitude sicknessPainful neuropathyTime-dependent increaseFiber injuryClinical onsetGanglion neuronsOxygen species productionSystem disordersCalcium levelsClinical reportsDistal extremitiesIntracellular Ca2NeuropathyNav1.7 channels
2006
A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons
Rush AM, Dib-Hajj SD, Liu S, Cummins TR, Black JA, Waxman SG. A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 8245-8250. PMID: 16702558, PMCID: PMC1472458, DOI: 10.1073/pnas.0602813103.Peer-Reviewed Original ResearchConceptsNeuronal cell typesCell typesChannel mutationsSympathetic neuronsMembrane potentialDifferent cell typesSodium channel mutationsMolecular basisNeuropathic pain syndromesIon channel mutationsSympathetic ganglion neuronsTypes of neuronsSingle mutationSodium channel Nav1.7Ion channelsMutationsPain syndromeSympathetic dysfunctionGanglion neuronsNav1.8 channelsSensory neuronsFunctional effectsChannel Nav1.7HypoexcitabilityNeurons