2018
Nonmuscle myosin II isoforms interact with sodium channel alpha subunits
Dash B, Han C, Waxman S, Dib-Hajj S. Nonmuscle myosin II isoforms interact with sodium channel alpha subunits. Molecular Pain 2018, 14: 1744806918788638. PMID: 29956586, PMCID: PMC6052497, DOI: 10.1177/1744806918788638.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAnkyrinsBrainCell Line, TransformedElectric StimulationGanglia, SpinalGene Expression RegulationGreen Fluorescent ProteinsHumansImmunoprecipitationMiceMice, Inbred C57BLMice, TransgenicMolecular Motor ProteinsMyosin Heavy ChainsNAV1.6 Voltage-Gated Sodium ChannelNonmuscle Myosin Type IIBPatch-Clamp TechniquesRatsTransfectionConceptsSodium channel alpha subunitND7/23 cellsChannel alpha subunitDorsal root ganglion tissueAlpha subunitMyosin II motor proteinsNonmuscle myosin II isoformsRodent nervous tissueRodent brain tissueSteady-state fast inactivationVoltage-sensitive channelsFast inactivationVoltage-dependent activationSodium channel alphaGanglion tissueIsoform-dependent mannerMyosin II isoformsNervous tissueRecombinant myosinBrain tissueCommon structural motifRamp currentsMotor proteinsCellular excitabilitySodium channels
2015
De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy
Blanchard MG, Willemsen MH, Walker JB, Dib-Hajj SD, Waxman SG, Jongmans M, Kleefstra T, van de Warrenburg BP, Praamstra P, Nicolai J, Yntema HG, Bindels R, Meisler MH, Kamsteeg EJ. De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy. Journal Of Medical Genetics 2015, 52: 330. PMID: 25725044, PMCID: PMC4413743, DOI: 10.1136/jmedgenet-2014-102813.Peer-Reviewed Original ResearchMeSH KeywordsAdultAmino Acid SequenceAmino Acid SubstitutionCell LineChildEpilepsyFemaleGenetic Association StudiesGenotypeHumansIntellectual DisabilityMaleMutationNAV1.6 Voltage-Gated Sodium ChannelPhenotypeProtein SubunitsConceptsClinical exome sequencingClinical featuresEarly-infantile epileptic encephalopathy type 13Intellectual disabilityVoltage-gated sodium channel Nav1.6De novo SCN8A mutationFunction mutationsExome sequencingSodium channel Nav1.6Variable clinical featuresGenotype-phenotype correlationSCN8A mutationsChannel Nav1.6Hyperpolarising shiftMutant sodium channelsPatientsDe novoHeterozygous lossSodium channelsElectrophysiological analysisClinical interpretationType 13DisabilitySeizuresWildtype channel
2014
Physiological and genetic analysis of multiple sodium channel variants in a model of genetic absence epilepsy
Oliva MK, McGarr TC, Beyer BJ, Gazina E, Kaplan DI, Cordeiro L, Thomas E, Dib-Hajj SD, Waxman SG, Frankel WN, Petrou S. Physiological and genetic analysis of multiple sodium channel variants in a model of genetic absence epilepsy. Neurobiology Of Disease 2014, 67: 180-190. PMID: 24657915, PMCID: PMC4298829, DOI: 10.1016/j.nbd.2014.03.007.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsBrainDisease Models, AnimalEpilepsy, AbsenceMiceMice, Inbred C3HMice, Inbred C57BLMice, Mutant StrainsModels, NeurologicalNAV1.2 Voltage-Gated Sodium ChannelNAV1.6 Voltage-Gated Sodium Channel
2009
The ataxia3 Mutation in the N-Terminal Cytoplasmic Domain of Sodium Channel Nav1.6 Disrupts Intracellular Trafficking
Sharkey LM, Cheng X, Drews V, Buchner DA, Jones JM, Justice MJ, Waxman SG, Dib-Hajj SD, Meisler MH. The ataxia3 Mutation in the N-Terminal Cytoplasmic Domain of Sodium Channel Nav1.6 Disrupts Intracellular Trafficking. Journal Of Neuroscience 2009, 29: 2733-2741. PMID: 19261867, PMCID: PMC2679640, DOI: 10.1523/jneurosci.6026-08.2009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCell LineChromosome MappingCytoplasmData Interpretation, StatisticalDNA, ComplementaryElectrophysiologyEthylnitrosoureaImmunohistochemistryMachado-Joseph DiseaseMiceMice, Inbred C57BLMutagensMutationMutation, MissenseNAV1.6 Voltage-Gated Sodium ChannelNerve Tissue ProteinsPatch-Clamp TechniquesSciatic NerveSodium ChannelsSubcellular FractionsTransfectionConceptsMutant channelsCytoplasmic N-terminal regionN-terminal cytoplasmic domainCytoplasmic N-terminal domainMouse chromosome 15N-terminal domainN-terminal regionAmino acid substitution p.Primary cerebellar granule cellsVoltage-dependent inward sodium currentMutant proteinsCytoplasmic domainJuvenile lethalityCis-GolgiTrafficking defectsPlasma membraneSodium channelsIntracellular traffickingProtein abundanceWild typeN-terminusGolgi complexMutant transcriptsChromosome 15Whole-cell patch-clamp studies
2006
Axonal conduction and injury in multiple sclerosis: the role of sodium channels
Waxman SG. Axonal conduction and injury in multiple sclerosis: the role of sodium channels. Nature Reviews Neuroscience 2006, 7: 932-941. PMID: 17115075, DOI: 10.1038/nrn2023.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAxonsHumansMultiple SclerosisMyelin SheathNAV1.6 Voltage-Gated Sodium ChannelNerve Fibers, MyelinatedNerve Tissue ProteinsNeural ConductionSodium ChannelsWallerian DegenerationConceptsAxonal degenerationSodium channelsChannel isoformsDistinct pathophysiological rolesKey PointsMultiple sclerosisMultiple neurological deficitsRelapsing-remitting courseRestoration of conductionDegeneration of axonsCerebellar Purkinje neuronsVoltage-gated sodium channelsContext of demyelinationNeurological deficitsProgressive courseMultiple sclerosisAxonal conductionDisease progressionNav1.8 channelsConduction failurePathophysiological rolePurkinje neuronsCNS axonsFiring patternsLoss of coordinationAberrant expression