2020
Excitable Membrane Properties of Neurons
Kaczmarek L. Excitable Membrane Properties of Neurons. 2020, 3-32. DOI: 10.1093/oxfordhb/9780190669164.013.20.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2019
Loss of NaV1.2-Dependent Backpropagating Action Potentials in Dendrites Contributes to Autism and Intellectual Disability
Kaczmarek LK. Loss of NaV1.2-Dependent Backpropagating Action Potentials in Dendrites Contributes to Autism and Intellectual Disability. Neuron 2019, 103: 551-553. PMID: 31437449, DOI: 10.1016/j.neuron.2019.07.032.Peer-Reviewed Original ResearchAn Epilepsy-Associated KCNT1 Mutation Enhances Excitability of Human iPSC-Derived Neurons by Increasing Slack KNa Currents
Quraishi IH, Stern S, Mangan KP, Zhang Y, Ali SR, Mercier MR, Marchetto MC, McLachlan MJ, Jones EM, Gage FH, Kaczmarek LK. An Epilepsy-Associated KCNT1 Mutation Enhances Excitability of Human iPSC-Derived Neurons by Increasing Slack KNa Currents. Journal Of Neuroscience 2019, 39: 7438-7449. PMID: 31350261, PMCID: PMC6759030, DOI: 10.1523/jneurosci.1628-18.2019.Peer-Reviewed Original ResearchConceptsSevere epileptic encephalopathyAction potentialsEpileptic encephalopathyFiring rateCurrent-clamp recordingsSodium-activated potassium channelsMaximal firing rateIntensity of firingMean firing rateKCNT1 mutationsCortical neuronsCell-autonomous mechanismsEffective treatmentHuman neuronsPotassium currentActive neuronsNeuronsPotassium channelsCompensatory changesDisease-causing mutationsHyperexcitabilityHuman iPSCEncephalopathyExcitabilityStem cellsModulators of Kv3 Potassium Channels Rescue the Auditory Function of Fragile X Mice
El-Hassar L, Song L, Tan WJT, Large CH, Alvaro G, Santos-Sacchi J, Kaczmarek LK. Modulators of Kv3 Potassium Channels Rescue the Auditory Function of Fragile X Mice. Journal Of Neuroscience 2019, 39: 4797-4813. PMID: 30936239, PMCID: PMC6561694, DOI: 10.1523/jneurosci.0839-18.2019.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAuditory PathwaysAuditory PerceptionBrain StemCochlear NucleusElectrophysiological PhenomenaEvoked Potentials, Auditory, Brain StemFemaleFragile X Mental Retardation ProteinFragile X SyndromeHydantoinsIn Vitro TechniquesMaleMiceMice, KnockoutPatch-Clamp TechniquesPyridinesShaw Potassium ChannelsConceptsAuditory brainstem responseWild-type animalsRepetitive firingABR wave ICurrent-clamp recordingsAuditory brainstem nucleiVoltage-clamp recordingsHigh-frequency firingSingle action potentialFragile X syndromeTrapezoid bodyBrainstem nucleiBrainstem responseMedial nucleusAuditory brainstemAuditory nerveWave IWave IVAction potentialsSensory stimuliKv3.1 channelsCentral processingMental retardation proteinHigh sound levelsMice
2017
Kv3 Channels: Enablers of Rapid Firing, Neurotransmitter Release, and Neuronal Endurance
Kaczmarek LK, Zhang Y. Kv3 Channels: Enablers of Rapid Firing, Neurotransmitter Release, and Neuronal Endurance. Physiological Reviews 2017, 97: 1431-1468. PMID: 28904001, PMCID: PMC6151494, DOI: 10.1152/physrev.00002.2017.Peer-Reviewed Original ResearchConceptsKv3 channelsAuditory brain stem neuronsNeurotransmitter releaseBrain stem neuronsOngoing neuronal activityFire action potentialsHigh-frequency firingChannel genesStem neuronsGABAergic interneuronsMultiple protein isoformsCertain neuronsProtein-protein interactionsNeuronal activityNeuronal functionAlzheimer's diseaseNeurological disordersAction potentialsPurkinje cellsUnique expression patternKv3 familyNeuronsAbnormal regulationProtein isoformsProtein kinaseAn ALS-Associated Mutant SOD1 Rapidly Suppresses KCNT1 (Slack) Na+-Activated K+ Channels in Aplysia Neurons
Zhang Y, Ni W, Horwich AL, Kaczmarek LK. An ALS-Associated Mutant SOD1 Rapidly Suppresses KCNT1 (Slack) Na+-Activated K+ Channels in Aplysia Neurons. Journal Of Neuroscience 2017, 37: 2258-2265. PMID: 28119399, PMCID: PMC5338764, DOI: 10.1523/jneurosci.3102-16.2017.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAplysiaBiophysicsCells, CulturedElectric StimulationEnzyme InhibitorsGanglia, InvertebrateHumansLuminescent ProteinsMembrane PotentialsMicroinjectionsMorpholinosMutationNerve Tissue ProteinsNeuronsPatch-Clamp TechniquesPotassium ChannelsPotassium Channels, Sodium-ActivatedRNA, Small InterferingSodiumSuperoxide Dismutase-1ConceptsAmyotrophic lateral sclerosisSuperoxide dismutase 1Mutant superoxide dismutase 1Potassium currentC-Jun N-terminal kinaseNeuronal excitabilityLateral sclerosisFatal adult-onset neurodegenerative diseaseN-terminal kinaseMutant human Cu/ZnNeuronal developmentDismutase 1Adult-onset neurodegenerative diseaseCurrent-clamp recordingsMotor neuron toxicityOutward potassium currentHuman Cu/ZnWild-type superoxide dismutase 1Neuron toxicityActivity of NaBag cell neuronsClamp recordingsNeuronal functionCell neuronsAction potentials
2016
Physiological modulators of Kv3.1 channels adjust firing patterns of auditory brain stem neurons
Brown MR, El-Hassar L, Zhang Y, Alvaro G, Large CH, Kaczmarek LK. Physiological modulators of Kv3.1 channels adjust firing patterns of auditory brain stem neurons. Journal Of Neurophysiology 2016, 116: 106-121. PMID: 27052580, PMCID: PMC4961756, DOI: 10.1152/jn.00174.2016.Peer-Reviewed Original ResearchConceptsKv3.1 channelsAuditory brain stem neuronsAuditory brain stemBrain stem neuronsBrain slice recordingsKv3.1 potassium channelVoltage of activationMNTB neuronsStem neuronsTrapezoid bodyBrain stemMedial nucleusKv3.1 currentsNeuronal excitabilitySlice recordingsTherapeutic benefitImidazolidinedione derivativesAction potentialsPhysiological modulatorPotassium channelsResting potentialsNeuronsSingle-channel recordingsChinese hamster ovary cellsPharmaceutical modulation
2015
Electrical Signaling in Neurons
Levitan I, Kaczmarek L. Electrical Signaling in Neurons. 2015, 41-62. DOI: 10.1093/med/9780199773893.003.0003.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMembrane Ion Channels and Ion Currents
Levitan I, Kaczmarek L. Membrane Ion Channels and Ion Currents. 2015, 63-84. DOI: 10.1093/med/9780199773893.003.0004.ChaptersSingle ion channelsIon currentMovement of ionsIon channelsParticular ionPlasma membraneSpecialized membrane proteinsMembrane ion channelsIonsAction potential firingNeuronal plasma membranePatch-clamp techniqueMembrane proteinsNeurons resultsCurrentClamp techniqueAction potentialsDetailed characterizationElectrical activityMembrane currentsMembrane voltageChannelsMacroscopic membrane currentsEssential propertiesComplex patternsFormation, Maintenance, and Plasticity of Chemical Synapses
Levitan I, Kaczmarek L. Formation, Maintenance, and Plasticity of Chemical Synapses. 2015, 415-456. DOI: 10.1093/med/9780199773893.003.0017.ChaptersAppropriate postsynaptic targetsPostsynaptic action potentialsImmediate early gene FosPostsynaptic receptorsPostsynaptic targetsNMDA receptorsExcitatory neuronsExcitatory synapsesPostsynaptic sitesPresynaptic terminalsPostsynaptic partnersAction potentialsNeuromuscular junctionSynapse formationCertain synapsesChemical synapsesAdult animalsElectrical activitySynapsesReceptorsBiochemical changesMental retardation proteinEph receptorsCoordinated activitySuch reorganizationIntrinsic Neuronal Properties, Neural Networks, and Behavior
Levitan I, Kaczmarek L. Intrinsic Neuronal Properties, Neural Networks, and Behavior. 2015, 457-488. DOI: 10.1093/med/9780199773893.003.0018.ChaptersAction of neurotransmittersIntrinsic neuronal propertiesIntrinsic excitabilityStomatogastric ganglionCommand neuronsNeuronal propertiesDendritic treeAction potentialsNeuronsCellular mechanismsNetwork activitySensory informationIntrinsic electrical propertiesGangliaExcitabilityMost behaviorsNeurotransmittersHormoneSynaptic Release of Neurotransmitters
Levitan I, Kaczmarek L. Synaptic Release of Neurotransmitters. 2015, 187-212. DOI: 10.1093/med/9780199773893.003.0009.ChaptersSynaptic vesiclesIndividual synaptic vesiclesRapid synaptic transmissionGenetic experimentsVoltage-dependent channelsEntry of calciumAmount of transmitterRelease of neurotransmittersSquid stellate ganglionFrog neuromuscular junctionNeurotransmitter releasePhysiological experimentsStellate ganglionSpecific synapsesSpecialized synapsesSynaptic transmissionSynaptic releaseRepetitive stimulationVesiclesPresynaptic terminalsNeuromuscular junctionAction potentialsFurther insightNeurotransmittersExocytosis
2013
Slack, Slick, and Sodium‐Activated Potassium Channels
Kaczmarek LK. Slack, Slick, and Sodium‐Activated Potassium Channels. International Scholarly Research Notices 2013, 2013: 354262. PMID: 24319675, PMCID: PMC3850776, DOI: 10.1155/2013/354262.Peer-Reviewed Original ResearchSodium-activated potassium currentPotassium channelsMore action potentialsCentral nervous systemAMPA receptorsNeuronal plasticityNative neuronsNervous systemNeurotransmitter receptorsSlick channelsIntracellular sodiumPotassium currentAction potentialsIntellectual functionSlack channelsReceptorsHuman mutationsSevere defectsCentral roleNeurons
2012
Regulation of Neuronal Excitability by Interaction of Fragile X Mental Retardation Protein with Slack Potassium Channels
Zhang Y, Brown MR, Hyland C, Chen Y, Kronengold J, Fleming MR, Kohn AB, Moroz LL, Kaczmarek LK. Regulation of Neuronal Excitability by Interaction of Fragile X Mental Retardation Protein with Slack Potassium Channels. Journal Of Neuroscience 2012, 32: 15318-15327. PMID: 23115170, PMCID: PMC3518385, DOI: 10.1523/jneurosci.2162-12.2012.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnisomycinAplysiaCHO CellsCloning, MolecularCricetinaeCricetulusElectrophysiological PhenomenaFragile X Mental Retardation ProteinImmunohistochemistryImmunoprecipitationNeuronsPatch-Clamp TechniquesPotassium ChannelsProtein Synthesis InhibitorsRNA InterferenceRNA, Small InterferingSodiumSynapsesConceptsNeuronal excitabilitySlack potassium channelsTetrodotoxin-sensitive componentCurrent-clamp recordingsSlack channelsMental retardation proteinBag cell neuronsSustained componentIntracellular injectionNeuronal firingInhibitory periodSynaptic stimulationPotassium currentCell neuronsAction potentialsOutward currentsPotassium channelsProlonged changesNeuronsAplysia bag cell neuronsProtein synthesis inhibitor anisomycinExcitabilityFragile X Mental Retardation ProteinCommon formIntellectual disabilityGradients and Modulation of K+ Channels Optimize Temporal Accuracy in Networks of Auditory Neurons
Kaczmarek LK. Gradients and Modulation of K+ Channels Optimize Temporal Accuracy in Networks of Auditory Neurons. PLOS Computational Biology 2012, 8: e1002424. PMID: 22438799, PMCID: PMC3305353, DOI: 10.1371/journal.pcbi.1002424.Peer-Reviewed Original ResearchConceptsSpontaneous activityPotassium currentRandom spontaneous activityAuditory brainstem neuronsAuditory brainstem nucleiSubset of neuronsMaximal firing rateHigh rateNormal auditory processingPattern of stimulationBrainstem neuronsBrainstem nucleiSynaptic outputAuditory neuronsChannel expressionSuch neuronsStimulus rateAction potentialsTonotopic axisSound stimulationFiring ratePotassium conductanceNeuronsKv3 channelsIndividual neurons
2010
Specific and rapid effects of acoustic stimulation on the tonotopic distribution of Kv3.1b potassium channels in the adult rat
Strumbos J, Polley D, Kaczmarek L. Specific and rapid effects of acoustic stimulation on the tonotopic distribution of Kv3.1b potassium channels in the adult rat. Neuroscience 2010, 167: 567-572. PMID: 20219640, PMCID: PMC2854512, DOI: 10.1016/j.neuroscience.2010.02.046.Peer-Reviewed Original ResearchMeSH KeywordsAcoustic StimulationAdaptation, PhysiologicalAnimalsAntibody SpecificityAuditory PathwaysAuditory ThresholdImmunohistochemistryIon Channel GatingNerve Tissue ProteinsNeuronal PlasticityRatsRats, Sprague-DawleyReaction TimeRhombencephalonShaw Potassium ChannelsSound LocalizationSynaptic TransmissionTime FactorsUp-RegulationConceptsTotal cellular levelsCytoplasmic C-terminusCellular levelVoltage-gated potassium channel subunitsPotassium channel subunitsTonotopic distributionAdult ratsC-terminusChannel proteinsChannel subunitsSound localization circuitIon channelsProteinExperience-dependent plasticityCultured neuronsPotassium channelsHigh-frequency stimuliAcute slicesMedial nucleusSynaptic activityAuditory neuronsKv3.1 proteinMin of exposureAction potentialsAcoustic stimulation
2008
Repetitive Firing Triggers Clustering of Kv2.1 Potassium Channels in Aplysia Neurons*
Zhang Y, McKay SE, Bewley B, Kaczmarek LK. Repetitive Firing Triggers Clustering of Kv2.1 Potassium Channels in Aplysia Neurons*. Journal Of Biological Chemistry 2008, 283: 10632-10641. PMID: 18276591, DOI: 10.1074/jbc.m800253200.Peer-Reviewed Original ResearchConceptsBag cell neuronsKv2.1 channelsPotassium channelsPlasma membraneC-terminusKv2.1 clustersKv2.1 potassium channelCell neuronsMammalian neuronsReproductive behaviorRectifier potassium channelFrequency-dependent broadeningRapid redistributionAplysia neuronsClamp recordingsAcid peptidePartial inactivationRing-like clustersPhysiological changesKv2.1Neuronal excitabilityCentral nervous systemAction potentialsGenesNervous system
2007
Sodium‐dependent potassium channels of a Slack‐like subtype contribute to the slow afterhyperpolarization in lamprey spinal neurons
Wallén P, Robertson B, Cangiano L, Löw P, Bhattacharjee A, Kaczmarek LK, Grillner S. Sodium‐dependent potassium channels of a Slack‐like subtype contribute to the slow afterhyperpolarization in lamprey spinal neurons. The Journal Of Physiology 2007, 585: 75-90. PMID: 17884929, PMCID: PMC2375474, DOI: 10.1113/jphysiol.2007.138156.Peer-Reviewed Original ResearchConceptsSodium-dependent potassium channelSlow afterhyperpolarizationAction potentialsPotassium channelsSingle action potentialLamprey spinal neuronsLamprey spinal cordLamprey locomotor networkSlow AHPLarge neuronsSpinal neuronsSpinal cordLocomotor networksBurst activityKNa channelsDistinct immunoreactivityGray matterReversal potentialNeuronsChloride injectionAfterhyperpolarizationRapid activationFunctional roleHigh-level activitiesSlack geneSlack and Slick KNa Channels Regulate the Accuracy of Timing of Auditory Neurons
Yang B, Desai R, Kaczmarek LK. Slack and Slick KNa Channels Regulate the Accuracy of Timing of Auditory Neurons. Journal Of Neuroscience 2007, 27: 2617-2627. PMID: 17344399, PMCID: PMC6672517, DOI: 10.1523/jneurosci.5308-06.2007.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAnimals, NewbornAuditory PathwaysBithionolBrain StemComputer SimulationElectric ConductivityElectric StimulationElectrophysiologyIn Vitro TechniquesMiceModels, NeurologicalNerve Tissue ProteinsNeuronsNeurons, AfferentPotassium ChannelsPotassium Channels, Sodium-ActivatedReaction TimeSodium
2005
Acoustic environment determines phosphorylation state of the Kv3.1 potassium channel in auditory neurons
Song P, Yang Y, Barnes-Davies M, Bhattacharjee A, Hamann M, Forsythe ID, Oliver DL, Kaczmarek LK. Acoustic environment determines phosphorylation state of the Kv3.1 potassium channel in auditory neurons. Nature Neuroscience 2005, 8: 1335-1342. PMID: 16136041, DOI: 10.1038/nn1533.Peer-Reviewed Original ResearchMeSH KeywordsAcoustic StimulationAction PotentialsAnimalsAnimals, NewbornBrain StemCHO CellsCricetinaeCricetulusDose-Response Relationship, RadiationElectric StimulationEnzyme InhibitorsFunctional LateralityGene Expression RegulationImmunohistochemistryIn Vitro TechniquesIndolesMaleimidesNeuronsPatch-Clamp TechniquesPhosphorylationProtein Kinase CRatsRats, Sprague-DawleyTetradecanoylphorbol AcetateConceptsKv3.1 potassium channelAction potentialsAuditory neuronsPotassium channelsShort-duration action potentialsRat brainstem neuronsAuditory brainstem nucleiProtein kinase CHigh-frequency spikingHigh-frequency auditoryBrainstem neuronsHigh-frequency stimuliBrainstem nucleiSynaptic stimulationNeuronsInteraural differencesSound localizationIntrinsic electrical propertiesKinase C