2024
Functionally-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 recordingsEndocannabinoidCannabinoidCompartment-specific regulation of NaV1.7 in sensory neurons after acute exposure to TNF-α
Tyagi S, Higerd-Rusli G, Ghovanloo M, Dib-Hajj F, Zhao P, Liu S, Kim D, Shim J, Park K, Waxman S, Choi J, Dib-Hajj S. Compartment-specific regulation of NaV1.7 in sensory neurons after acute exposure to TNF-α. Cell Reports 2024, 43: 113685. PMID: 38261513, PMCID: PMC10947185, DOI: 10.1016/j.celrep.2024.113685.Peer-Reviewed Original ResearchTNF-aSensory neuronsEffect of TNF-aSensory neuron excitabilityTumor necrosis factor-aRegulation of NaV1.7Voltage-gated sodiumPro-inflammatory cytokinesCompartment-specific effectsNeuronal plasma membraneSensitize nociceptorsNeuronal excitabilitySomatic membraneChannel N terminusElectrophysiological recordingsP38 MAPKIon channelsFactor AAcute exposureMolecular determinantsNeuronsAxonal endingsPhospho-acceptor sitesPlasma membraneCompartment-specific regulation
2023
Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function
Jami S, Deuis J, Klasfauseweh T, Cheng X, Kurdyukov S, Chung F, Okorokov A, Li S, Zhang J, Cristofori-Armstrong B, Israel M, Ju R, Robinson S, Zhao P, Ragnarsson L, Andersson Å, Tran P, Schendel V, McMahon K, Tran H, Chin Y, Zhu Y, Liu J, Crawford T, Purushothamvasan S, Habib A, Andersson D, Rash L, Wood J, Zhao J, Stehbens S, Mobli M, Leffler A, Jiang D, Cox J, Waxman S, Dib-Hajj S, Neely G, Durek T, Vetter I. Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function. Nature Communications 2023, 14: 2442. PMID: 37117223, PMCID: PMC10147923, DOI: 10.1038/s41467-023-37963-2.Peer-Reviewed Original ResearchConceptsSensory neuronsVoltage-sensing domainNav channelsTransmembrane proteinAccessory proteinsVoltage-gated sodium channelsCritical regulatorPore domainChannel gatingExtracellular loopToxin-mediated effectsNeuronal excitabilityPeptide toxinsProteinSodium channelsPharmacological activitiesNav1.7 functionKnottin peptidesNeuronsImportant insightsToxinSubunitsRegulatorDomainExcelsa
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 firingInjuryDepolarizing NaV and Hyperpolarizing KV Channels Are Co-Trafficked in Sensory Neurons
Higerd-Rusli GP, Alsaloum M, Tyagi S, Sarveswaran N, Estacion M, Akin EJ, Dib-Hajj FB, Liu S, Sosniak D, Zhao P, Dib-Hajj SD, Waxman SG. Depolarizing NaV and Hyperpolarizing KV Channels Are Co-Trafficked in Sensory Neurons. Journal Of Neuroscience 2022, 42: 4794-4811. PMID: 35589395, PMCID: PMC9188389, DOI: 10.1523/jneurosci.0058-22.2022.Peer-Reviewed Original ResearchIon channel traffickingMembrane proteinsChannel traffickingAxonal membrane proteinsTransport vesiclesPhysiological functionsSame vesiclesAxonal proteinsSpecific transport vesiclesIon channelsTrafficking of NaDiverse physiological functionsExcitability disordersDifferent physiological functionsDistinct ion channelsSensory neuron membraneSensory neuronsDistinct functional classesDistinct functional rolesNormal neuronal excitabilityTrafficking mechanismsNeuronal excitabilityPlasma membraneTherapeutic strategiesPrecise regulation
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
2005
Intermittent hypoxia modulates Na+ channel expression in developing mouse brain
Zhao P, Xue J, Gu X, Haddad G, Xia Y. Intermittent hypoxia modulates Na+ channel expression in developing mouse brain. International Journal Of Developmental Neuroscience 2005, 23: 327-333. PMID: 15927756, DOI: 10.1016/j.ijdevneu.2004.12.011.Peer-Reviewed Original Research
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