2020
Differential effect of lacosamide on Nav1.7 variants from responsive and non-responsive patients with small fibre neuropathy
Labau J, Estacion M, Tanaka BS, de Greef B, Hoeijmakers J, Geerts M, Gerrits MM, Smeets H, Faber CG, Merkies I, Lauria G, Dib-Hajj SD, Waxman SG. Differential effect of lacosamide on Nav1.7 variants from responsive and non-responsive patients with small fibre neuropathy. Brain 2020, 143: 771-782. PMID: 32011655, PMCID: PMC7089662, DOI: 10.1093/brain/awaa016.Peer-Reviewed Original ResearchConceptsSmall fiber neuropathyEffects of lacosamideNon-responsive patientsSubset of patientsCommon pain disordersRecent clinical studiesUse-dependent inhibitionUse-dependent mannerVoltage-clamp recordingsPotent sodium channel inhibitorSlow inactivationSodium channel inhibitorsNeuronal hyperexcitabilityResponsive patientsPain disordersNav1.7 mutationClinical studiesAchievable concentrationsPatientsLacosamideNeuropathyChannel inhibitorsSodium channelsPainFunction mutations
2016
Nav1.7-A1632G Mutation from a Family with Inherited Erythromelalgia: Enhanced Firing of Dorsal Root Ganglia Neurons Evoked by Thermal Stimuli
Yang Y, Huang J, Mis MA, Estacion M, Macala L, Shah P, Schulman BR, Horton DB, Dib-Hajj SD, Waxman SG. Nav1.7-A1632G Mutation from a Family with Inherited Erythromelalgia: Enhanced Firing of Dorsal Root Ganglia Neurons Evoked by Thermal Stimuli. Journal Of Neuroscience 2016, 36: 7511-7522. PMID: 27413160, PMCID: PMC6705539, DOI: 10.1523/jneurosci.0462-16.2016.Peer-Reviewed Original ResearchConceptsRat DRG neuronsDorsal root ganglion neuronsDRG neuronsCurrent-clamp recordingsSodium channel Nav1.7Pain syndromeNav1.7 mutationGanglion neuronsThermal stimuliIEM patientsChannel Nav1.7Whole-cell current-clamp recordingsNav1.7 channelsFunction Nav1.7 mutationsSevere pain syndromeVoltage-gated sodium channel Nav1.7Voltage-clamp recordingsMutant Nav1.7 channelsMean firing frequencyMultielectrode array recordingsMutant channelsG mutationMultigeneration familySpontaneous firingSympathetic neuronsPharmacotherapy for Pain in a Family With Inherited Erythromelalgia Guided by Genomic Analysis and Functional Profiling
Geha P, Yang Y, Estacion M, Schulman BR, Tokuno H, Apkarian AV, Dib-Hajj SD, Waxman SG. Pharmacotherapy for Pain in a Family With Inherited Erythromelalgia Guided by Genomic Analysis and Functional Profiling. JAMA Neurology 2016, 73: 659. PMID: 27088781, DOI: 10.1001/jamaneurol.2016.0389.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAdultAnalgesics, Non-NarcoticBrainCarbamazepineChronic PainDNA Mutational AnalysisDouble-Blind MethodElectric StimulationErythromelalgiaFemaleGanglia, SpinalHumansMagnetic Resonance ImagingMaleMutationNAV1.7 Voltage-Gated Sodium ChannelPain MeasurementRegression AnalysisSensory Receptor CellsConceptsMean episode durationDRG neuronsPatient 1Nav1.7 mutationEpisode durationDorsal root ganglion neuronsPlacebo-controlled studyMaintenance periodAttenuation of painEffects of carbamazepineBrain activityFunctional magnetic resonance imagingMagnetic resonance imagingT mutationMutant channelsFunctional magnetic resonanceNeuropathic painSecondary somatosensoryChronic painPain areaPatient 2Ganglion neuronsEffective pharmacotherapyNight awakeningsPlacebo
2011
Intra- and Interfamily Phenotypic Diversity in Pain Syndromes Associated with a Gain-of-Function Variant of NaV1.7
Estación M, Han C, Choi JS, Hoeijmakers J, Lauria G, Drenth J, Gerrits MM, Dib-Hajj SD, Faber CG, Merkies I, Waxman SG. Intra- and Interfamily Phenotypic Diversity in Pain Syndromes Associated with a Gain-of-Function Variant of NaV1.7. Molecular Pain 2011, 7: 1744-8069-7-92. PMID: 22136189, PMCID: PMC3248882, DOI: 10.1186/1744-8069-7-92.Peer-Reviewed Original ResearchConceptsParoxysmal extreme pain disorderSmall fiber neuropathyDorsal root gangliaInherited ErythromelalgiaPain syndromeFunction variantsTrigeminal ganglionIdiopathic small fiber neuropathySevere facial painQuantitative sensory testingSympathetic ganglion neuronsDifferent clinical presentationsSodium channel Nav1.7Distal painNeuropathic painFacial painAutonomic symptomsDRG neuronsPain disordersClinical presentationClinical pictureSyndrome AssociatedGanglion neuronsRoot gangliaSkin biopsies
2010
A sodium channel mutation linked to epilepsy increases ramp and persistent current of Nav1.3 and induces hyperexcitability in hippocampal neurons
Estacion M, Gasser A, Dib-Hajj SD, Waxman SG. A sodium channel mutation linked to epilepsy increases ramp and persistent current of Nav1.3 and induces hyperexcitability in hippocampal neurons. Experimental Neurology 2010, 224: 362-368. PMID: 20420834, DOI: 10.1016/j.expneurol.2010.04.012.Peer-Reviewed Original ResearchConceptsHippocampal neuronsCardiac muscle sodium channelsCryptogenic partial epilepsyHippocampal neuron excitabilitySodium channelsSomatic pain disordersDifferent sodium channel isoformsHuman chromosome 2Sodium channel isoformsPain disordersPartial epilepsyNeuron excitabilityPathophysiological basisExcitability disordersSpontaneous firingSodium channel mutationsGene SCN1ASodium channelopathiesCharge-neutralizing mutationsRamp currentsMuscle sodium channelsChromosome 2Channel isoformsChannel mutationsFunctional analysis
2008
NaV1.7 Gain-of-Function Mutations as a Continuum: A1632E Displays Physiological Changes Associated with Erythromelalgia and Paroxysmal Extreme Pain Disorder Mutations and Produces Symptoms of Both Disorders
Estacion M, Dib-Hajj SD, Benke PJ, Morsche R, Eastman EM, Macala LJ, Drenth JP, Waxman SG. NaV1.7 Gain-of-Function Mutations as a Continuum: A1632E Displays Physiological Changes Associated with Erythromelalgia and Paroxysmal Extreme Pain Disorder Mutations and Produces Symptoms of Both Disorders. Journal Of Neuroscience 2008, 28: 11079-11088. PMID: 18945915, PMCID: PMC6671384, DOI: 10.1523/jneurosci.3443-08.2008.Peer-Reviewed Original ResearchMeSH KeywordsAlanineAnimalsAnimals, NewbornCells, CulturedChildDose-Response Relationship, RadiationElectric StimulationErythromelalgiaGanglia, SpinalGlutamic AcidHumansMaleMembrane PotentialsModels, MolecularMutationNAV1.7 Voltage-Gated Sodium ChannelNeuronsPatch-Clamp TechniquesRatsRats, Sprague-DawleySodium ChannelsSomatoform DisordersTime FactorsTransfectionConceptsParoxysmal extreme pain disorderDorsal root gangliaTrigeminal ganglion neuronsClinical phenotypeGanglion neuronsMixed clinical phenotypePersistent inward currentsFunction mutationsPatch-clamp analysisPEPD mutationsPain disordersFast inactivationRoot gangliaInward currentsDistinct disordersCurrent clampErythromelalgiaDisordersPainChannel functionVoltage dependencePhysiological changesNeuronsIEMPhenotype
2004
Association of Immunophilins with Mammalian TRPC Channels*
Sinkins W, Goel M, Estacion M, Schilling W. Association of Immunophilins with Mammalian TRPC Channels*. Journal Of Biological Chemistry 2004, 279: 34521-34529. PMID: 15199065, DOI: 10.1074/jbc.m401156200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBaculoviridaeBrainCalcium ChannelsCell LineDose-Response Relationship, DrugElectrophysiologyGlutamineHumansImmunoblottingImmunophilinsInsectaMutationPeptidesPrecipitin TestsProlineProtein BindingProtein Structure, TertiaryRatsTacrolimus Binding Protein 1ATacrolimus Binding ProteinsTime FactorsTRPC Cation ChannelsConceptsTRPC channel proteinsChannel proteinsMammalian TRPC channelsTRPC channelsHEK cellsBinding of FKBP12Rat brain lysatesImmunosuppressant drug FK506Receptor-mediated activationSf9 cellsAccessory proteinsRat cerebral cortexImmunophilinsDrug FK506Brain lysatesFKBP52FKBP12Membrane lysatesGln mutationINADProteinFKBP59SignalplexTRPC1Cerebral cortex
2001
Regulation of Drosophila TRPL Channels by Immunophilin FKBP59*
Goel M, Garcia R, Estacion M, Schilling W. Regulation of Drosophila TRPL Channels by Immunophilin FKBP59*. Journal Of Biological Chemistry 2001, 276: 38762-38773. PMID: 11514552, DOI: 10.1074/jbc.m104125200.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceAnimalsBinding SitesCalciumCalmodulin-Binding ProteinsCationsCell LineChelating AgentsDNA, ComplementaryDrosophilaDrosophila ProteinsEgtazic AcidElectrophysiologyGene LibraryGlutathione TransferaseHumansImmunohistochemistryInsectaMembrane ProteinsMicroscopy, FluorescenceMolecular Sequence DataMutationPhotoreceptor Cells, InvertebratePolymerase Chain ReactionPrecipitin TestsProtein BindingProtein Structure, TertiaryRecombinant ProteinsSequence Homology, Amino AcidSignal TransductionTacrolimus Binding ProteinsTime FactorsTransient Receptor Potential ChannelsTwo-Hybrid System TechniquesConceptsS2 cellsTRPL channelsDrosophila head cDNA libraryDrosophila photoreceptor cellsHuman FK506-binding proteinMultimeric signaling complexesTwo-hybrid screenDrosophila S2 cellsDrosophila TRPL channelsSf9 cell lysatesFK506-binding proteinChannel activitySite-directed mutagenesisCytoplasmic membrane surfaceFura-2 assayTransient receptor potentialDrosophila homologPermeable cation channelSignaling ComplexNovel proteinCDNA librarySf9 cellsINADCytoplasmic mouthChannel regulation
1997
Mutations Causing Achondroplasia and Thanatophoric Dysplasia Alter bFGF-Induced Calcium Signals in Human Diploid Fibroblasts
Nguyen H, Estacion M, Gargus J. Mutations Causing Achondroplasia and Thanatophoric Dysplasia Alter bFGF-Induced Calcium Signals in Human Diploid Fibroblasts. Human Molecular Genetics 1997, 6: 681-688. PMID: 9158142, DOI: 10.1093/hmg/6.5.681.Peer-Reviewed Original ResearchMeSH KeywordsAchondroplasiaBradykininCalciumCell LineDiploidyFibroblast Growth Factor 2FibroblastsHomozygoteHumansMutationProtein-Tyrosine KinasesReceptor Protein-Tyrosine KinasesReceptor, Fibroblast Growth Factor, Type 1Receptor, Fibroblast Growth Factor, Type 2Receptor, Fibroblast Growth Factor, Type 3Receptors, Fibroblast Growth FactorRNA SplicingSignal TransductionThanatophoric DysplasiaConceptsThanatophoric dysplasiaCalcium signalsBasic fibroblast growth factorCell linesCalcium-imaging analysesFibroblast growth factorFibroblast growth factor receptor (FGFR) gene familyHuman diploid fibroblastsPathophysiological mechanismsIntracellular calciumBlinded studyFGFR3 mutationsUnresponsive linesReceptor functionHereditary disorderTransient increaseGrowth factorDiploid fibroblastsControl cellsBone developmentFibroblast cell lineCalcium wavesReceptor gene familyHeterogeneous signalsAchondroplasia