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 insightsToxinSubunitsRegulatorDomainExcelsaHigh-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
Inhibition 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
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
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 studies
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