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 generationNav1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis
Fu W, Vasylyev D, Bi Y, Zhang M, Sun G, Khleborodova A, Huang G, Zhao L, Zhou R, Li Y, Liu S, Cai X, He W, Cui M, Zhao X, Hettinghouse A, Good J, Kim E, Strauss E, Leucht P, Schwarzkopf R, Guo E, Samuels J, Hu W, Attur M, Waxman S, Liu C. Nav1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis. Nature 2024, 625: 557-565. PMID: 38172636, PMCID: PMC10794151, DOI: 10.1038/s41586-023-06888-7.Peer-Reviewed Original ResearchVoltage-gated sodium channelsOA progressionDorsal root ganglion neuronsStructural joint damagePain relief treatmentHuman OA chondrocytesCommon joint diseaseMultiple mouse modelsNav1.7 blockersPain behaviorGanglion neuronsPharmacological blockadeJoint damageJoint degenerationChannel blockersJoint diseaseOA chondrocytesMouse modelTherapeutic targetOsteoarthritisIntracellular Ca2Nav1.7Nav1.7 channelsGenetic ablationLimited evidence
2018
Nav1.7 is phosphorylated by Fyn tyrosine kinase which modulates channel expression and gating in a cell type-dependent manner
Li Y, Zhu T, Yang H, Dib-Hajj S, Waxman S, Yu Y, Xu TL, Cheng X. Nav1.7 is phosphorylated by Fyn tyrosine kinase which modulates channel expression and gating in a cell type-dependent manner. Molecular Pain 2018, 14: 1744806918782229. PMID: 29790812, PMCID: PMC6024516, DOI: 10.1177/1744806918782229.Peer-Reviewed Original ResearchConceptsND7/23 cellsDRG neuron excitabilityModulation of Nav1.7New pain therapeuticsVoltage-gated sodium channel Nav1.7Fyn kinaseWhole-cell recordingsSodium channel Nav1.7Elevated protein expressionCell type-specific modulationHuman embryonic kidney 293 cellsTyrosine kinasePain disordersEmbryonic kidney 293 cellsPain therapeuticsNeuron excitabilityPain perceptionMutant channelsChannel Nav1.7Kidney 293 cellsNav1.7HEK-293 cellsNav1.7 channelsCell type-dependent mannerType-dependent manner
2013
A new Nav1.7 mutation in an erythromelalgia patient
Estacion M, Yang Y, Dib-Hajj SD, Tyrrell L, Lin Z, Yang Y, Waxman SG. A new Nav1.7 mutation in an erythromelalgia patient. Biochemical And Biophysical Research Communications 2013, 432: 99-104. PMID: 23376079, DOI: 10.1016/j.bbrc.2013.01.079.Peer-Reviewed Original ResearchConceptsMutations of Nav1.7Voltage-gated sodium channel Nav1.7Year old patientSodium channel Nav1.7Voltage-clamp studiesErythromelalgia patientsOlder patientsDRG neuronsNav1.7 mutationPainful disordersFunction missense mutationsChannel Nav1.7Neuron firingPatientsRamp stimuliExon 20Channel biophysical propertiesControl allelesNav1.7Missense mutationsBiophysical propertiesMutations
2006
Mutations in the sodium channel Nav1.7 underlie inherited erythromelalgia
Dib-Hajj S, Rush A, Cummins T, Waxman S. Mutations in the sodium channel Nav1.7 underlie inherited erythromelalgia. Drug Discovery Today Disease Mechanisms 2006, 3: 343-350. DOI: 10.1016/j.ddmec.2006.09.005.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsSympathetic ganglion neuronsDorsal root gangliaHigh-frequency firingSingle action potentialSodium channel Nav1.7Mild thermal stimuliSevere painDRG neuronsPainful conditionsGanglion neuronsRoot gangliaChannel Nav1.7Action potentialsModel diseaseThermal stimuliErythromelalgiaNeuronsMutant channelsFunctional studiesIEMPainGangliaNav1.7MutationsDisease