2024
Molecular 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 channels
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
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 ResearchLate 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 propertiesNerveSeizuresArrhythmiasChannelopathiesDisease
2020
Cannabidiol 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 channels
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 channelsA Mixed Periodic Paralysis & Myotonia Mutant, P1158S, Imparts pH-Sensitivity in Skeletal Muscle Voltage-gated Sodium Channels
Ghovanloo MR, Abdelsayed M, Peters CH, Ruben PC. A Mixed Periodic Paralysis & Myotonia Mutant, P1158S, Imparts pH-Sensitivity in Skeletal Muscle Voltage-gated Sodium Channels. Scientific Reports 2018, 8: 6304. PMID: 29674667, PMCID: PMC5908869, DOI: 10.1038/s41598-018-24719-y.Peer-Reviewed Original ResearchConceptsPeriodic paralysisSkeletal muscle voltageSkeletal muscle channelopathiesHypokalemic periodic paralysisSteady-state fast inactivationLow potassium levelsAutosomal dominant mutationsEpisodic attacksIntense exercisePhysical activityMuscle channelopathiesBlood acidosisCommon triggerPotassium levelsAction potential modelingParalysisSodium channelsMuscular contractionSkeletal muscleMyotoniaPhenotype correlationLate currentPatientsExtracellular pHFast inactivationpH Modulation of Voltage-Gated Sodium Channels
Peters CH, Ghovanloo MR, Gershome C, Ruben PC. pH Modulation of Voltage-Gated Sodium Channels. Handbook Of Experimental Pharmacology 2018, 246: 147-160. PMID: 29460150, DOI: 10.1007/164_2018_99.Peer-Reviewed Original ResearchConceptsElectrical diseaseSodium channelsChannel gatingDisease-causing mutantsSodium channel poreTransient sodium currentModulation of VoltageIschemic strokeNon-inactivating channelsSkeletal muscle sodium channelsAcute symptomsCocaine ingestionCardiac ischemiaSodium channel mutationsMuscle sodium channelsSodium currentIsoform specificitySodium channel gatingTissue-level effectsPathophysiological conditionsChannel mutationsSkeletal muscleDiseaseCardiac tissueChannel poreEffects 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
2016
Chapter Fifteen Physiology and Pathophysiology of Sodium Channel Inactivation
Ghovanloo MR, Aimar K, Ghadiry-Tavi R, Yu A, Ruben PC. Chapter Fifteen Physiology and Pathophysiology of Sodium Channel Inactivation. Current Topics In Membranes 2016, 78: 479-509. PMID: 27586293, DOI: 10.1016/bs.ctm.2016.04.001.Peer-Reviewed Original ResearchEffects of Amiodarone and N-desethylamiodarone on Cardiac Voltage-Gated Sodium Channels
Ghovanloo MR, Abdelsayed M, Ruben PC. Effects of Amiodarone and N-desethylamiodarone on Cardiac Voltage-Gated Sodium Channels. Frontiers In Pharmacology 2016, 7: 39. PMID: 26973526, PMCID: PMC4771766, DOI: 10.3389/fphar.2016.00039.Peer-Reviewed Original ResearchEffects of amiodaronePro-arrhythmic effectsAntiarrhythmic drugsN-desethylamiodaroneLate sodium currentPotent antiarrhythmic drugDrug-mediated effectsAdverse side effectsAtrial fibrillationPharmacologic profileQT intervalAmiodaroneSide effectsCardiac voltageWindow currentSodium currentClass ISodium channelsHigh efficacyDrugsPeak conductanceNav1.5Similar profilesTorsadesTachycardia