2000
A double mutation in families with periodic paralysis defines new aspects of sodium channel slow inactivation
Bendahhou S, Cummins T, Hahn A, Langlois S, Waxman S, Ptácek L. A double mutation in families with periodic paralysis defines new aspects of sodium channel slow inactivation. Journal Of Clinical Investigation 2000, 106: 431-438. PMID: 10930446, PMCID: PMC314328, DOI: 10.1172/jci9654.Peer-Reviewed Original ResearchConceptsChannel slow inactivationPeriodic paralysisSlow inactivationSodium channel slow inactivationMalignant hyperthermia susceptibilitySkeletal muscle disordersHuman skeletal muscleParalytic attacksMuscle disordersHyperkalemic periodic paralysisSkeletal muscleParalysisDisease-causing mutationsNovel mutationsHyperKPPChannel defectsMolecular determinantsAlpha subunitMutant channelsMutationsDouble mutationInactivationPatientsTransmembrane segments S5
1999
Characterization of a new sodium channel mutation at arginine 1448 associated with moderate paramyotonia congenita in humans
Bendahhou S, Cummins T, Kwiecinski H, Waxman S, Ptácek L. Characterization of a new sodium channel mutation at arginine 1448 associated with moderate paramyotonia congenita in humans. The Journal Of Physiology 1999, 518: 337-344. PMID: 10381583, PMCID: PMC2269438, DOI: 10.1111/j.1469-7793.1999.0337p.x.Peer-Reviewed Original ResearchConceptsChannel functionMutant channelsHuman embryonic kidney 293 cellsEmbryonic kidney 293 cellsSodium channel alpha subunitAmino acid changesSingle nucleotide substitutionKidney 293 cellsChannel alpha subunitSkeletal muscle voltage-gated sodium channelPosition 1448Sodium channel mutationsParamyotonia congenitaVoltage-gated sodium channelsSodium channel functionNucleotide substitutionsAlpha subunitSingle-strand conformation polymorphism analysisSegment S4Skeletal muscle disordersDomain IVAcid changesNew genetic mutationsDNA sequencingFast inactivationActivation and Inactivation of the Voltage-Gated Sodium Channel: Role of Segment S5 Revealed by a Novel Hyperkalaemic Periodic Paralysis Mutation
Bendahhou S, Cummins T, Tawil R, Waxman S, Ptácek L. Activation and Inactivation of the Voltage-Gated Sodium Channel: Role of Segment S5 Revealed by a Novel Hyperkalaemic Periodic Paralysis Mutation. Journal Of Neuroscience 1999, 19: 4762-4771. PMID: 10366610, PMCID: PMC6782655, DOI: 10.1523/jneurosci.19-12-04762.1999.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedDNA Mutational AnalysisDNA PrimersGene ExpressionHumansHyperkalemiaIon Channel GatingKidneyKineticsMaleMiddle AgedMolecular Sequence DataNAV1.4 Voltage-Gated Sodium ChannelParalyses, Familial PeriodicPatch-Clamp TechniquesPoint MutationProtein Structure, TertiarySequence Homology, Amino AcidSodium ChannelsTransfectionConceptsSegments S5Point mutationsS5 segmentVoltage-Gated Sodium ChannelSodium channelsTransmembrane segments S5Cytoplasmic interfaceWild-type channelsParalysis phenotypeHomologous domainsVoltage-sensitive sodium channelsPotassium-aggravated myotoniaNew point mutationPhenylalanine substitutionSkeletal muscle disordersHyperkalaemic periodic paralysisFast inactivationSecond domainMutationsGenesChannel deactivationInactivationChannel activationSlow inactivationT704M mutation
1998
Slow Closed-State Inactivation: A Novel Mechanism Underlying Ramp Currents in Cells Expressing the hNE/PN1 Sodium Channel
Cummins T, Howe J, Waxman S. Slow Closed-State Inactivation: A Novel Mechanism Underlying Ramp Currents in Cells Expressing the hNE/PN1 Sodium Channel. Journal Of Neuroscience 1998, 18: 9607-9619. PMID: 9822722, PMCID: PMC6793269, DOI: 10.1523/jneurosci.18-23-09607.1998.Peer-Reviewed Original ResearchConceptsTTX-S currentsRamp currentsDRG neuronsClosed-state inactivationSensory neuronsChannel isoformsDistinct integrative propertiesSmall DRG neuronsSodium channelsTTX-sensitive currentsSlow ramp depolarizationSteady-state inactivationRamp depolarizationNeuronsSkeletal muscleState inactivationIntegrative propertiesInactivation propertiesOpen-state inactivationExcitable cellsNovel mechanismCellsDepolarizationInactivationPN1
1997
Differential Effects of NGF and BDNF on Axotomy-Induced Changes in GABAA-Receptor-Mediated Conductance and Sodium Currents in Cutaneous Afferent Neurons
Oyelese A, Rizzo M, Waxman S, Kocsis J. Differential Effects of NGF and BDNF on Axotomy-Induced Changes in GABAA-Receptor-Mediated Conductance and Sodium Currents in Cutaneous Afferent Neurons. Journal Of Neurophysiology 1997, 78: 31-42. PMID: 9242258, PMCID: PMC2605357, DOI: 10.1152/jn.1997.78.1.31.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factorCutaneous afferent neuronsNerve growth factorReceptor-mediated conductanceProportion of neuronsAfferent neuronsAction potential waveformSodium currentNeurotrophic factorL4/L5 DRG neuronsAction potentialsVoltage-dependent sodium currentsWhole-cell patch-clamp techniqueDorsal root ganglion neuronsCell patch-clamp techniqueAxotomy-induced increaseFluoro-Gold injectionsL5 DRG neuronsSpecific neurotrophic factorsSciatic nerve stumpsTTX-sensitive currentsInjury-induced changesResistant sodium currentsGamma-aminobutyric acidPatch-clamp techniqueTTX-Sensitive and -Resistant Na+ Currents, and mRNA for the TTX-Resistant rH1 Channel, Are Expressed in B104 Neuroblastoma Cells
Gu X, Dib-Hajj S, Rizzo M, Waxman S. TTX-Sensitive and -Resistant Na+ Currents, and mRNA for the TTX-Resistant rH1 Channel, Are Expressed in B104 Neuroblastoma Cells. Journal Of Neurophysiology 1997, 77: 236-246. PMID: 9120565, DOI: 10.1152/jn.1997.77.1.236.Peer-Reviewed Original ResearchConceptsB104 neuroblastoma cellsTTX-resistant channelsB104 cellsNeuroblastoma cellsWhole-cell patch-clamp methodAbsence of TTXTTX-resistant currentTTX-sensitive currentsPresence of TTXPA/pFTranscription-polymerase chain reactionLong QT syndromeCell linesSteady-state inactivationNeuroblastoma cell linesAlpha-subunit mRNAPatch-clamp methodTTX-sensitiveHalf-maximal inhibitionInactivation time constantsChannel mRNATTXMembrane excitabilitySubunit mRNAsRT-PCR
1992
Ionic mechanisms of anoxic injury in mammalian CNS white matter: role of Na+ channels and Na(+)-Ca2+ exchanger
Stys P, Waxman S, Ransom B. Ionic mechanisms of anoxic injury in mammalian CNS white matter: role of Na+ channels and Na(+)-Ca2+ exchanger. Journal Of Neuroscience 1992, 12: 430-439. PMID: 1311030, PMCID: PMC6575619, DOI: 10.1523/jneurosci.12-02-00430.1992.Peer-Reviewed Original ResearchConceptsRat optic nerveCompound action potentialAnoxic injuryOptic nerveWhite matterAction potentialsCentral white matter tractsWhite matter injuryCNS white matterMembrane depolarizationAnoxia/ischemiaWhite matter tractsCNS protectionAnoxic insultMyelinated tractsChannel blockersExchanger blockerIrreversible injuryExtracellular Ca2Mammalian CNSNerveInjuryMore injuriesBlockersFunctional integrity
1986
Mammalian optic nerve fibers display two pharmacologically distinct potassium channels
Kocsis J, Gordon T, Waxman S. Mammalian optic nerve fibers display two pharmacologically distinct potassium channels. Brain Research 1986, 383: 357-361. PMID: 2429732, DOI: 10.1016/0006-8993(86)90040-5.Peer-Reviewed Original ResearchConceptsOptic nerve fibersNerve fibersDistinct potassium channelsPotassium channelsRat optic nerve fibersNerve action potentialsAction potential characteristicsAction potential repolarizationTEA-sensitive channelsIntracellular hyperpolarizationAction potentialsPotential repolarizationSuction electrodeTetraethylammoniumPotential characteristicsRepolarizationPositivity