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 recordingsEndocannabinoidCannabinoid
2023
Nav1.7 P610T mutation in two siblings with persistent ocular pain after corneal axon transection: impaired slow inactivation and hyperexcitable trigeminal neurons
Ghovanloo M, Effraim P, Yuan J, Schulman B, Jacobs D, Dib-Hajj S, Waxman S. Nav1.7 P610T mutation in two siblings with persistent ocular pain after corneal axon transection: impaired slow inactivation and hyperexcitable trigeminal neurons. Journal Of Neurophysiology 2023, 129: 609-618. PMID: 36722722, PMCID: PMC9988530, DOI: 10.1152/jn.00457.2022.Peer-Reviewed Original ResearchConceptsPersistent ocular painTrigeminal ganglion neuronsOcular painCorneal refractive surgeryGanglion neuronsRefractive surgeryAxonal injurySlow inactivationHuman pain modelTrigeminal afferent nervesTrigeminal ganglion axonsSmall subgroupPain-related disordersEffects of injurySodium channel Nav1.7Channel slow inactivationEye painPostoperative painMost patientsPain modelAfferent nervesPersistent painTrigeminal neuronsNav1.7 mutationAxon transectionHigh-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
2018
Inhibitory effects of cannabidiol on voltage-dependent sodium currents
Ghovanloo MR, Shuart NG, Mezeyova J, Dean RA, Ruben PC, Goodchild SJ. Inhibitory effects of cannabidiol on voltage-dependent sodium currents. Journal Of Biological Chemistry 2018, 293: 16546-16558. PMID: 30219789, PMCID: PMC6204917, DOI: 10.1074/jbc.ra118.004929.Peer-Reviewed Original ResearchConceptsAnticonvulsant effectsVoltage-dependent sodium currentsPotassium channelsSafety of cannabidiolNav channelsCentral nervous system targetsEffects of cannabidiolNervous system targetsVoltage-dependent currentsVoltage-gated potassium channelsVoltage-clamp electrophysiologyAntiepileptic effectClinical efficacyCase reportAlters membrane fluidityIPSC-neuronsTherapeutic mechanismSodium currentHEK-293 cellsReceptor pathwayΔ9-tetrahydrocannabinolInhibitory effectCannabidiolChannel excitabilitySodium channelsEffects of acidosis on neuronal voltage-gated sodium channels: Nav1.1 and Nav1.3
Ghovanloo MR, Peters CH, Ruben PC. Effects of acidosis on neuronal voltage-gated sodium channels: Nav1.1 and Nav1.3. Channels 2018, 12: 367-377. PMID: 30362397, PMCID: PMC6284583, DOI: 10.1080/19336950.2018.1539611.Peer-Reviewed Original ResearchConceptsSodium channel subtypesVoltage-gated sodium channelsChannel subtypesNeuronal voltage-gated sodium channelsSodium channelsEffect of acidosisSteady-state fast inactivationPH-sensitive channelsNeonatal neuronsFast inactivationAdult neuronsInhibitory neuronsPathophysiological manifestationsNav1.3Nav1.1Membrane excitabilityExtracellular acidosisNeuronsSubtypesAcidosisModerate reductionExtracellular pHTissue-specific mannerKey contributorExcitability