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 generationFunctionally-selective inhibition of threshold sodium currents and excitability in dorsal root ganglion neurons by cannabinol
Ghovanloo M, Effraim P, Tyagi S, Zhao P, Dib-Hajj S, Waxman S. Functionally-selective inhibition of threshold sodium currents and excitability in dorsal root ganglion neurons by cannabinol. Communications Biology 2024, 7: 120. PMID: 38263462, PMCID: PMC10805714, DOI: 10.1038/s42003-024-05781-x.Peer-Reviewed Original ResearchConceptsDorsal root ganglionDorsal root ganglion neuronal excitabilityDorsal root ganglion neuronsNeuronal excitabilityCurrent-clamp analysisSteady-state inactivationVoltage-dependent sodiumSlow inactivated stateAutomated patch clamp platformMultielectrode array recordingsNav currentsNeuropathic painSodium currentRoot ganglionGanglion neuronsSlow inactivationInactivated stateCurrent inhibitorsIon channelsNeuronsInhibitory effectCannabinolArray recordingsEndocannabinoidCannabinoid
2023
High-throughput combined voltage-clamp/current-clamp analysis of freshly isolated neurons
Ghovanloo M, Tyagi S, Zhao P, Kiziltug E, Estacion M, Dib-Hajj S, Waxman S. High-throughput combined voltage-clamp/current-clamp analysis of freshly isolated neurons. Cell Reports Methods 2023, 3: 100385. PMID: 36814833, PMCID: PMC9939380, DOI: 10.1016/j.crmeth.2022.100385.Peer-Reviewed Original ResearchConceptsDorsal root ganglion neuronsCurrent-clamp recordingsCurrent-clamp analysisVoltage-gated sodium channelsPatch-clamp techniqueExcitable cellsGanglion neuronsElectrophysiological recordingsNeuronal cellsNeuronsGold standard methodologySodium channelsCellular levelRobotic instrumentsCellsDrug screeningSame cellsIntact tissueRecordings
2022
Fibroblast growth factor homologous factor 2 attenuates excitability of DRG neurons
Effraim PR, Estacion M, Zhao P, Sosniak D, Waxman SG, Dib-Hajj SD. Fibroblast growth factor homologous factor 2 attenuates excitability of DRG neurons. Journal Of Neurophysiology 2022, 128: 1258-1266. PMID: 36222860, PMCID: PMC9909838, DOI: 10.1152/jn.00361.2022.Peer-Reviewed Original ResearchConceptsDRG neuron excitabilityDRG neuronal excitabilityNeuronal excitabilityFibroblast growth factor homologous factorsNerve injuryDRG neuronsInflammatory mediatorsNeuron excitabilityDorsal root ganglion neuronsFunction of Nav1.7Peripheral nerve axotomyMultiple neurological disordersVoltage-gated sodium channelsDRG excitabilityFibroblast growth factor homologous factor 2Inflammatory painNerve axotomyGanglion neuronsIsoform-dependent mannerNeurological disordersBasal conditionsExcitabilityGating propertiesNeuron firingInjuryInhibition of sodium conductance by cannabigerol contributes to a reduction of dorsal root ganglion neuron excitability
Ghovanloo M, Estacion M, Higerd‐Rusli G, Zhao P, Dib‐Hajj S, Waxman SG. Inhibition of sodium conductance by cannabigerol contributes to a reduction of dorsal root ganglion neuron excitability. British Journal Of Pharmacology 2022, 179: 4010-4030. PMID: 35297036, DOI: 10.1111/bph.15833.Peer-Reviewed Original ResearchConceptsEffect of cannabigerolDRG neuronsDorsal root ganglion neuron excitabilityVoltage-gated sodium currentDorsal root ganglion neuronsLower CBG concentrationPrimary dorsal root ganglion neuronsAnalgesic drug developmentNon-psychotropic phytocannabinoidMultielectrode array recordingsAction potential modellingInhibition of NaDRG excitabilityGanglion neuronsNeuron excitabilityAnalgesic propertiesCNS neuronsNeuronal hypoexcitabilityCBG concentrationsChannel inhibitorsSodium currentNeuronsFunctional selectivityDrug developmentUnderlying mechanism
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
2014
Dynamic-clamp analysis of wild-type human Nav1.7 and erythromelalgia mutant channel L858H
Vasylyev DV, Han C, Zhao P, Dib-Hajj S, Waxman SG. Dynamic-clamp analysis of wild-type human Nav1.7 and erythromelalgia mutant channel L858H. Journal Of Neurophysiology 2014, 111: 1429-1443. PMID: 24401712, DOI: 10.1152/jn.00763.2013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiophysicsCells, CulturedElectric StimulationErythromelalgiaGanglia, SpinalHEK293 CellsHumansMembrane PotentialsMiceMice, KnockoutModels, BiologicalMutationNAV1.7 Voltage-Gated Sodium ChannelNeural ConductionNeuronsPatch-Clamp TechniquesSodium Channel BlockersTetrodotoxinTransfectionConceptsDRG neuronsMutant Nav1.7 channelsNav1.7 channelsDorsal root ganglion neuronsSodium influxPrimary nociceptive neuronsSmall DRG neuronsNet sodium influxSodium channel Nav1.7Current thresholdMechanistic linkAction potential generationNeuropathic painNociceptive neuronsNociceptor functionGanglion neuronsNociceptor hyperexcitabilityPain phenotypesChannel expressionChannel Nav1.7Subthreshold depolarizationHuman Nav1.7Electrophysiological recordingsDynamic-Clamp AnalysisIdentification of gain
2013
Small-Fiber Neuropathy Nav1.8 Mutation Shifts Activation to Hyperpolarized Potentials and Increases Excitability of Dorsal Root Ganglion Neurons
Huang J, Yang Y, Zhao P, Gerrits MM, Hoeijmakers JG, Bekelaar K, Merkies IS, Faber CG, Dib-Hajj SD, Waxman SG. Small-Fiber Neuropathy Nav1.8 Mutation Shifts Activation to Hyperpolarized Potentials and Increases Excitability of Dorsal Root Ganglion Neurons. Journal Of Neuroscience 2013, 33: 14087-14097. PMID: 23986244, PMCID: PMC6618513, DOI: 10.1523/jneurosci.2710-13.2013.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAmino Acid SequenceAnimalsCells, CulturedGanglia, SpinalHumansIon Channel GatingMaleMembrane PotentialsMiceMice, TransgenicMiddle AgedMolecular Sequence DataMutation, MissenseNAV1.8 Voltage-Gated Sodium ChannelNeuronsPeripheral Nervous System DiseasesRatsRats, Sprague-DawleyConceptsDorsal root ganglion neuronsSmall DRG neuronsDRG neuronsGanglion neuronsAction potentialsIdiopathic small fiber neuropathySmall-diameter DRG neuronsWhole-cell voltage-clamp recordingsSmall-caliber nerve fibersVoltage-gated sodium channel Nav1.7Peripheral sensory neuronsCurrent-clamp studiesLimited treatment optionsSmall fiber neuropathySodium channel Nav1.8Voltage-clamp recordingsSodium channel Nav1.7Autonomic dysfunctionIncreases excitabilityTreatment optionsUnknown etiologyFunctional variantsNerve fibersSensory neuronsRamp depolarization
2007
Anisomycin protects cortical neurons from prolonged hypoxia with differential regulation of p38 and ERK
Hong SS, Qian H, Zhao P, Bazzy-Asaad A, Xia Y. Anisomycin protects cortical neurons from prolonged hypoxia with differential regulation of p38 and ERK. Brain Research 2007, 1149: 76-86. PMID: 17391655, PMCID: PMC1937507, DOI: 10.1016/j.brainres.2007.02.062.Peer-Reviewed Original ResearchConceptsDOR inhibitionCortical neuronsP38 immunoreactivityNeuronal injuryNeuronal responsesMAP kinase activityDelta opioid receptor signalingCultured cortical neuronsHypoxia-induced injuryNormoxic neuronsMAP kinaseNeuronal survivalNeuronal viabilitySurvival/deathSignificant injuryInjuryNaltrindoleCell survival/deathPhosphorylated p38Receptor signalingNeuronsImmunoreactivityHypoxiaPhosphorylated ERKLDH leakage
2006
Rapid Hypoxia Preconditioning Protects Cortical Neurons From Glutamate Toxicity Through δ-Opioid Receptor
Zhang J, Qian H, Zhao P, Hong SS, Xia Y. Rapid Hypoxia Preconditioning Protects Cortical Neurons From Glutamate Toxicity Through δ-Opioid Receptor. Stroke 2006, 37: 1094-1099. PMID: 16514101, DOI: 10.1161/01.str.0000206444.29930.18.Peer-Reviewed Original ResearchConceptsDelta-opioid receptorsHypoxia preconditioningCortical neuronsNeuronal injuryGlutamate-induced neuronal injuryCultured rat cortical neuronsReceptor bindingSevere hypoxic injurySevere neuronal injuryRT-PCRCultured cortical neuronsMRNA levelsNMDA receptor expressionRat cortical neuronsΔ-opioid receptorsDOR mRNA levelsCulture day 8Short-term hypoxiaDOR mRNALactate dehydrogenase leakageHypoxic injuryGlutamate toxicityNeuronal viabilityReceptor expressionNeuroprotection
2005
GABA and glycine are protective to mature but toxic to immature rat cortical neurons under hypoxia
Zhao P, Qian H, Xia Y. GABA and glycine are protective to mature but toxic to immature rat cortical neurons under hypoxia. European Journal Of Neuroscience 2005, 22: 289-300. PMID: 16045482, DOI: 10.1111/j.1460-9568.2005.04222.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCell CountCell DeathCell DifferentiationCell HypoxiaCells, CulturedCerebral CortexDose-Response Relationship, DrugDrug InteractionsEmbryo, MammalianEnkephalin, Leucine-2-AlanineGamma-Aminobutyric AcidGene Expression Regulation, DevelopmentalGlycineL-Lactate DehydrogenaseNeuronsRatsRats, Sprague-DawleyReceptors, GABA-AReceptors, GlycineReference ValuesTaurineTime FactorsConceptsGamma-aminobutyric acidRat cortical neuronsCortical neuronsInhibitory neurotransmitterHypoxic neuronsImmature neuronsHypoxic cortical neuronsDelta-opioid receptorsMajor inhibitory neurotransmitterHypoxic injuryNeuronal ageMature neuronsNeuronal responsesGlycine receptorsLong-term exposureNeuronsDifferential developmental profilesHypoxiaNeurotransmittersDevelopmental profileReceptorsTaurinePresent studyAgeRecent studiesOxygen-sensitive δ-Opioid Receptor-regulated Survival and Death Signals NOVEL INSIGHTS INTO NEURONAL PRECONDITIONING AND PROTECTION*
Ma M, Qian H, Ghassemi F, Zhao P, Xia Y. Oxygen-sensitive δ-Opioid Receptor-regulated Survival and Death Signals NOVEL INSIGHTS INTO NEURONAL PRECONDITIONING AND PROTECTION*. Journal Of Biological Chemistry 2005, 280: 16208-16218. PMID: 15687501, DOI: 10.1074/jbc.m408055200.Peer-Reviewed Original ResearchConceptsDelta-opioid receptorsHPC protectionSevere hypoxiaSpecific signaling pathwaysCytochrome c releaseP38 MAPK activityKinase C pathwayBcl-2 activityMembrane proteinsC releaseMAPK activityMolecular mechanismsSignaling pathwaysΔ-opioid receptorsP38 MAPKNovel insightsNovel mechanismC pathwayNeuronal injuryDOR antagonistDOR mRNAProtein levelsDOR expressionIschemic disordersNeuronal preconditioning
2003
Na+ Channel Expression and Neuronal Function in the Na+/H+ Exchanger 1 Null Mutant Mouse
Xia Y, Zhao P, Xue J, Gu X, Sun X, Yao H, Haddad G. Na+ Channel Expression and Neuronal Function in the Na+/H+ Exchanger 1 Null Mutant Mouse. Journal Of Neurophysiology 2003, 89: 229-236. PMID: 12522174, DOI: 10.1152/jn.00488.2002.Peer-Reviewed Original ResearchConceptsChannel expressionMutant miceCA1 neuronsMembrane excitabilityHippocampal CA1 neuronsNull mutant miceRecurrent seizuresCortical neuronsPrevious electrophysiological workNeuronal excitabilityEpileptic seizuresChannel upregulationNeuronal functionCortical regionsCortex formExcitabilityMiceSeizuresHippocampusSubtype IIAltered expressionNeuronsElectrophysiological workImmunoblotting techniquesSubtype I
2002
Neuroprotective role of δ-opioid receptors in cortical neurons
Zhang J, Gibney GT, Zhao P, Xia Y. Neuroprotective role of δ-opioid receptors in cortical neurons. American Journal Of Physiology - Cell Physiology 2002, 282: c1225-c1234. PMID: 11997236, DOI: 10.1152/ajpcell.00226.2001.Peer-Reviewed Original ResearchConceptsCortical neuronsNeuronal injuryHypoxic injuryReceptor activationKappa-opioid receptor inhibitionDelta-opioid receptor activationOpioid receptor activationCultured cortical neuronsGlutamate-induced injuryΔ-opioid receptorsLactate dehydrogenase releaseImmature neuronsNeuroprotective roleReceptor inhibitionHypoxic exposureNeuronal susceptibilityCell injuryDay 4InjuryDehydrogenase releaseNeuronsActivation/inhibitionHypoxiaHypoxic conditionsHypoxic stress