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
2018
Effects 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