2024
Impacts of resident physician unionization on house staff compensation
Tyagi S, Shah R, Huttler J, Kayani J, Ghovanloo M, Effraim P. Impacts of resident physician unionization on house staff compensation. PLOS ONE 2024, 19: e0308100. PMID: 39361626, PMCID: PMC11449312, DOI: 10.1371/journal.pone.0308100.Peer-Reviewed Original ResearchConceptsNon-union counterpartsPhysician unionsWorking long hoursUnion statusResidency training programsUnion programCost-of-livingLow wagesStaff compensationLong hoursTraining programSalaryInternal medicine residency training programsPhysicians-in-trainingRegional factorsDisbursementBenefit dataCross-sectional investigationMonetary benefitsUnionResident salariesCompensationCost-of-living differencesPGY-1Residency programsThe evolution of patch-clamp electrophysiology: robotic, multiplex, and dynamic.
Ghovanloo M, Dib-Hajj S, Waxman S. The evolution of patch-clamp electrophysiology: robotic, multiplex, and dynamic. Molecular Pharmacology 2024 PMID: 39164111, DOI: 10.1124/molpharm.124.000954.Peer-Reviewed Original ResearchPatch-clamp techniquePatch-clamp electrophysiologyPatch clampVoltage- and current-clamp modesIon channelsContribution of ion channelsCurrent-clamp modePatch-clamp methodOhm's lawDynamic-clampGating mechanisms of ion channelsMuscle cellsCardiac excitabilityGold standardExcitable cellsReceptorsGate conductionElectrophysiologyNeuronsElectrogenesisSimultaneous recordingCellsHigh-throughput automated platformMechanisms of ion channelsGating mechanismMolecular Pharmacology of Selective NaV1.6 and Dual NaV1.6/NaV1.2 Channel Inhibitors that Suppress Excitatory Neuronal Activity Ex Vivo
Goodchild S, Shuart N, Williams A, Ye W, Parrish R, Soriano M, Thouta S, Mezeyova J, Waldbrook M, Dean R, Focken T, Ghovanloo M, Ruben P, Scott F, Cohen C, Empfield J, Johnson J. Molecular Pharmacology of Selective NaV1.6 and Dual NaV1.6/NaV1.2 Channel Inhibitors that Suppress Excitatory Neuronal Activity Ex Vivo. ACS Chemical Neuroscience 2024, 15: 1169-1184. PMID: 38359277, PMCID: PMC10958515, DOI: 10.1021/acschemneuro.3c00757.Peer-Reviewed Original ResearchExcitatory pyramidal neuronsPyramidal neuronsNeuronal action potential firingSeizure modelsActivity of excitatory neuronsInhibition of firingAction potential firingVoltage-gated sodium channelsSuppress epileptiform activityTherapeutic safety marginActivity ex vivoNeuronal hyperexcitabilityInhibitory interneuronsChannel inhibitorsEpileptiform activityInhibitory neuronsPotential firingExcitatory neuronsAntiseizure medicationsExcitatory circuitsBrain slicesReduced excitabilityPharmacological dissectionAntiseizure medication carbamazepineSodium channelsTRPM8 mutations associated with persistent ocular pain after refractive surgery: D665N and V915M
Ghovanloo M, Effraim P, Tyagi S, Cheng X, Yuan J, Schulman B, Jacobs D, Dib-Hajj S, Waxman S. TRPM8 mutations associated with persistent ocular pain after refractive surgery: D665N and V915M. Biophysical Journal 2024, 123: 391a. DOI: 10.1016/j.bpj.2023.11.2376.Peer-Reviewed Original ResearchFunctionally-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
Sodium currents in naïve mouse dorsal root ganglion neurons: No major differences between sexes
Ghovanloo M, Tyagi S, Zhao P, Effraim P, Dib-Hajj S, Waxman S. Sodium currents in naïve mouse dorsal root ganglion neurons: No major differences between sexes. Channels 2023, 18: 2289256. PMID: 38055732, PMCID: PMC10761158, DOI: 10.1080/19336950.2023.2289256.Peer-Reviewed Original ResearchConceptsSexual dimorphismRodent dorsal root ganglion neuronsBiophysical propertiesDorsal root ganglion neuronsExpression patternsSex-dependent regulationVoltage-gated sodiumFunctional analysisGanglion neuronsRodent sensory neuronsMouse dorsal root ganglion neuronsNaïve WT miceNumber of cellsMixed populationDimorphismUniform experimental conditionsSex-dependent differencesSensory neuronsNative DRG neuronsPain pathwaysDRG neuronsWT miceClinical studiesNav currentsAdult malesEditorial: Cannabinoid interactions with ion channels, receptors, and the bio-membrane
Ghovanloo M, Arnold J, Ruben P. Editorial: Cannabinoid interactions with ion channels, receptors, and the bio-membrane. Frontiers In Physiology 2023, 14: 1211230. PMID: 37228821, PMCID: PMC10203607, DOI: 10.3389/fphys.2023.1211230.Peer-Reviewed Original ResearchNav1.7 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
Non-psychotropic phytocannabinoid interactions with voltage-gated sodium channels: An update on cannabidiol and cannabigerol
Ghovanloo M, Dib-Hajj S, Goodchild S, Ruben P, Waxman S. Non-psychotropic phytocannabinoid interactions with voltage-gated sodium channels: An update on cannabidiol and cannabigerol. Frontiers In Physiology 2022, 13: 1066455. PMID: 36439273, PMCID: PMC9691960, DOI: 10.3389/fphys.2022.1066455.Peer-Reviewed Original ResearchCannabidiol increases gramicidin current in human embryonic kidney cells: An observational study
Ghovanloo MR, Goodchild SJ, Ruben PC. Cannabidiol increases gramicidin current in human embryonic kidney cells: An observational study. PLOS ONE 2022, 17: e0271801. PMID: 35913948, PMCID: PMC9342711, DOI: 10.1371/journal.pone.0271801.Peer-Reviewed Original ResearchConceptsHuman embryonic kidney cellsEmbryonic kidney cellsHEK cell membranesMembrane biophysical propertiesKidney cellsMonomeric proteinCompound-protein interactionsBacterial cellsIon channelsCell membraneBiophysical propertiesLipid membranesFormation of poresCellsLinear gramicidinCannabis plantCBD activityMembraneGramicidinPlantsProteinPotential therapeutic propertiesLate sodium current: incomplete inactivation triggers seizures, myotonias, arrhythmias, and pain syndromes
Fouda MA, Ghovanloo M, Ruben PC. Late sodium current: incomplete inactivation triggers seizures, myotonias, arrhythmias, and pain syndromes. The Journal Of Physiology 2022, 600: 2835-2851. PMID: 35436004, DOI: 10.1113/jp282768.Peer-Reviewed Original ResearchConceptsLate sodium currentSodium currentSkeletal muscleAction potential durationRepetitive action potentialsVoltage-gated sodium channelsSeizure disorderTrigger seizuresPeripheral nervesPotential durationSodium channelopathiesAction potentialsSodium channelsChannel inactivationPainDysfunctionMyotoniaMuscleHeartGating propertiesNerveSeizuresArrhythmiasChannelopathiesDiseaseInhibition 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
Cannabidiol and Sodium Channel Pharmacology: General Overview, Mechanism, and Clinical Implications
Ghovanloo MR, Ruben PC. Cannabidiol and Sodium Channel Pharmacology: General Overview, Mechanism, and Clinical Implications. The Neuroscientist 2021, 28: 318-334. PMID: 34027742, PMCID: PMC9344566, DOI: 10.1177/10738584211017009.Peer-Reviewed Original ResearchConceptsClinical implicationsNav channelsPotential therapeutic meansInteractions of cannabidiolVoltage-gated sodiumSodium channel pharmacologyClinical syndromePreclinical studiesCBD useNeurological conditionsCBD interactionsChannel pharmacologyTherapeutic meansAction potentialsMuscular problemsPathophysiological conditionsCannabidiolChannel functionExcitable tissuesViable compoundCannabis plantTissueDifferent tissuesHyperexcitabilitySyndromeCannabidiol inhibits the skeletal muscle Nav1.4 by blocking its pore and by altering membrane elasticity
Ghovanloo MR, Choudhury K, Bandaru TS, Fouda MA, Rayani K, Rusinova R, Phaterpekar T, Nelkenbrecher K, Watkins AR, Poburko D, Thewalt J, Andersen OS, Delemotte L, Goodchild SJ, Ruben PC. Cannabidiol inhibits the skeletal muscle Nav1.4 by blocking its pore and by altering membrane elasticity. The Journal Of General Physiology 2021, 153: e202012701. PMID: 33836525, PMCID: PMC8042605, DOI: 10.1085/jgp.202012701.Peer-Reviewed Original Research
2020
Biophysical Characterization of a Novel SCN5A Mutation Associated With an Atypical Phenotype of Atrial and Ventricular Arrhythmias and Sudden Death
Ghovanloo MR, Atallah J, Escudero CA, Ruben PC. Biophysical Characterization of a Novel SCN5A Mutation Associated With an Atypical Phenotype of Atrial and Ventricular Arrhythmias and Sudden Death. Frontiers In Physiology 2020, 11: 610436. PMID: 33414724, PMCID: PMC7783455, DOI: 10.3389/fphys.2020.610436.Peer-Reviewed Original ResearchSudden cardiac deathCatecholaminergic polymorphic ventricular tachycardiaAtrial action potential durationCPVT-like phenotypeOnset of symptomsPolymorphic ventricular tachycardiaPrimary electrical disordersStrong family historyCardiac electrical propertiesAction potential durationNovel SCN5A mutationUse-dependent inactivationCardiac ion channelsO'Hara-Rudy modelCardiac deathVentricular arrhythmiasSCD casesTachy-arrhythmiasVentricular tachycardiaCannabidiol interactions with voltage-gated sodium channels
Sait LG, Sula A, Ghovanloo MR, Hollingworth D, Ruben PC, Wallace B. Cannabidiol interactions with voltage-gated sodium channels. ELife 2020, 9: e58593. PMID: 33089780, PMCID: PMC7641581, DOI: 10.7554/elife.58593.Peer-Reviewed Original ResearchConceptsVoltage-gated sodium channelsNavMs voltage-gated sodium channelHigh-resolution X-ray crystallographyIon translocation pathwaySodium channelsCentral hydrophobic cavitySodium channel mutationsTranslocation pathwayMolecular mechanismsNovel siteNovel insightsTRPV2 channelsTarget siteChannel mutationsX-ray crystallographyNon-psychoactive compoundFunctional effectsHydrophobic cavityCannabis plantChannel inhibitionSitesPlantsMutationsNeurological diseasesType of epilepsyCannabidiol protects against high glucose‐induced oxidative stress and cytotoxicity in cardiac voltage‐gated sodium channels
Fouda MA, Ghovanloo M, Ruben PC. Cannabidiol protects against high glucose‐induced oxidative stress and cytotoxicity in cardiac voltage‐gated sodium channels. British Journal Of Pharmacology 2020, 177: 2932-2946. PMID: 32077098, PMCID: PMC7279989, DOI: 10.1111/bph.15020.Peer-Reviewed Original ResearchConceptsHigh glucoseOxidative stressHigh glucose-induced oxidative stressCardiac voltage-gated sodium channelGlucose-induced oxidative stressReactive oxygen speciesCardiac sodium channel isoformChannel inhibitory effectVoltage-gated sodium channelsSteady-state fast inactivationHigh glucose conditionsSodium channel isoformsAction potential modellingDeleterious effectsCardiovascular complicationsDiabetic patientsAction potentialsCell viability assaysArrhythmiasMajor causeInhibitory effectChannel isoformsCannabidiolGlucose conditionsSodium channelsSay Cheese: Structure of the Cardiac Electrical Engine Is Captured
Ghovanloo MR, Ruben PC. Say Cheese: Structure of the Cardiac Electrical Engine Is Captured. Trends In Biochemical Sciences 2020, 45: 369-371. PMID: 32311330, DOI: 10.1016/j.tibs.2020.02.003.Peer-Reviewed Original Research