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 neuronsSubtype-Selective Small Molecule Inhibitors Reveal a Fundamental Role for Nav1.7 in Nociceptor Electrogenesis, Axonal Conduction and Presynaptic Release
Alexandrou AJ, Brown AR, Chapman ML, Estacion M, Turner J, Mis MA, Wilbrey A, Payne EC, Gutteridge A, Cox PJ, Doyle R, Printzenhoff D, Lin Z, Marron BE, West C, Swain NA, Storer RI, Stupple PA, Castle NA, Hounshell JA, Rivara M, Randall A, Dib-Hajj SD, Krafte D, Waxman SG, Patel MK, Butt RP, Stevens EB. Subtype-Selective Small Molecule Inhibitors Reveal a Fundamental Role for Nav1.7 in Nociceptor Electrogenesis, Axonal Conduction and Presynaptic Release. PLOS ONE 2016, 11: e0152405. PMID: 27050761, PMCID: PMC4822888, DOI: 10.1371/journal.pone.0152405.Peer-Reviewed Original ResearchConceptsPeripheral neuropeptide releaseSodium channel 1.7Dorsal hornPresynaptic releaseNociceptive signalingPain sensationAxonal conductionNeuropeptide releaseSpinal cordSynaptic transmissionPF-05089771Small molecule inhibitorsHuman nociceptorsAction potentialsNav1.7Nav1.7 inhibitorsUpstroke phaseHuman genetic studiesKey molecular determinantsNociceptorsSelective inhibitorMolecule inhibitorsRelative functional contributionInhibitorsFunctional contribution
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
Can robots patch‐clamp as well as humans? Characterization of a novel sodium channel mutation
Estacion M, Choi JS, Eastman EM, Lin Z, Li Y, Tyrrell L, Yang Y, Dib‐Hajj S, Waxman SG. Can robots patch‐clamp as well as humans? Characterization of a novel sodium channel mutation. The Journal Of Physiology 2010, 588: 1915-1927. PMID: 20123784, PMCID: PMC2901980, DOI: 10.1113/jphysiol.2009.186114.Peer-Reviewed Original ResearchA 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
2001
Regulation of Drosophila transient receptor potential‐like (TrpL) channels by phospholipase C‐dependent mechanisms
Estacion M, Sinkins W, Schilling W. Regulation of Drosophila transient receptor potential‐like (TrpL) channels by phospholipase C‐dependent mechanisms. The Journal Of Physiology 2001, 530: 1-19. PMID: 11136854, PMCID: PMC2278390, DOI: 10.1111/j.1469-7793.2001.0001m.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBaculoviridaeCalciumCalmodulin-Binding ProteinsCell LineCHO CellsCricetinaeDrosophilaDrosophila ProteinsFluorescent DyesFura-2Indicators and ReagentsMembrane PotentialsMembrane ProteinsOocytesPatch-Clamp TechniquesPhosphatidylinositol 4,5-DiphosphateSpodopteraTransient Receptor Potential ChannelsType C PhospholipasesXenopusConceptsPhospholipase CPhospholipase DDrosophila TRPL channelsTRPL channel activitySf9 insect cellsBacterial PI-PLCsPLC-dependent mechanismChannel activityFura-2 assayReceptor stimulationHydrolysis of PIP2Generation of diacylglycerolPoly-unsaturated fatty acidsTRPL channelsReceptor-mediated activationAddition of phosphatidylinositolInsect cellsExogenous applicationPI-PLCTransient receptor potential-like channelPC-PLCPIP2Spontaneous channel activityTRPLDiacylglycerol
1999
Stimulation of Drosophila TrpL by capacitative Ca2+ entry.
Estacion M, Sinkins W, Schilling W. Stimulation of Drosophila TrpL by capacitative Ca2+ entry. Biochemical Journal 1999, 341 ( Pt 1): 41-9. PMID: 10377243, PMCID: PMC1220328, DOI: 10.1042/0264-6021:3410041.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBariumBiological TransportCalciumCalcium-Transporting ATPasesCalmodulinCalmodulin-Binding ProteinsCations, DivalentDrosophilaDrosophila ProteinsEndoplasmic ReticulumHumansIon Channel GatingIon ChannelsLanthanumMembrane ProteinsPatch-Clamp TechniquesRecombinant Fusion ProteinsSpodopteraStrontiumThapsigarginTransient Receptor Potential ChannelsConceptsCapacitative Ca2Internal Ca2Receptor-activated channelsCell-attached patch recordingsTRP-like proteinsNon-selective cation channelsCytosolic free Ca2CBS-2Fura-2Cation entryPatch recordingsHuman TRPC1Single-channel activityDrosophila TRPLTRPL activityFree Ca2Dependent mechanismCation influxGel overlay experimentsCation channelsPhotoreceptor cellsChannel activityPhospholipase CTRPC1TRPL channel activity
1997
PDGF-Stimulated Calcium Influx Changes During In Vitro Cell Transformation
Estacion M, Mordan L. PDGF-Stimulated Calcium Influx Changes During In Vitro Cell Transformation. Cellular Signalling 1997, 9: 363-366. PMID: 9376215, DOI: 10.1016/s0898-6568(96)00184-2.Peer-Reviewed Original ResearchConceptsT-type calcium channelsCalcium signalsIntracellular calcium signalsC3H 10T1/2 mouse fibroblastsCalcium channelsPreneoplastic clonesMarked reductionGrowth factorMetabolism changesVitro Cell TransformationCell transformationColonies of cellsElectrophysiology measurementsInflux changeCellsMouse fibroblasts
1996
Calcium is permeable through a maitotoxin-activated nonselective cation channel in mouse L cells
Estacion M, Nguyen H, Gargus J. Calcium is permeable through a maitotoxin-activated nonselective cation channel in mouse L cells. American Journal Of Physiology 1996, 270: c1145-c1152. PMID: 8928742, DOI: 10.1152/ajpcell.1996.270.4.c1145.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCationsElectric ConductivityFibroblastsIon ChannelsL CellsMarine ToxinsMiceOxocinsPatch-Clamp TechniquesPotassiumConceptsNonselective cation channelsCation channelsCalcium-activated potassium channelsPlatelet-derived growth factorIntracellular calciumGrowth factor responseExtracellular calciumSecondary activationPotassium channelsGrowth factorFactor responseL cellsCell typesCalciumMouse L cellsL-cell fibroblastsMouse L-cell fibroblastsCell fibroblastsCellsIrreversible opening