2020
Impaired motor skill learning and altered seizure susceptibility in mice with loss or gain of function of the Kcnt1 gene encoding Slack (KNa1.1) Na+-activated K+ channels
Quraishi IH, Mercier MR, McClure H, Couture RL, Schwartz ML, Lukowski R, Ruth P, Kaczmarek LK. Impaired motor skill learning and altered seizure susceptibility in mice with loss or gain of function of the Kcnt1 gene encoding Slack (KNa1.1) Na+-activated K+ channels. Scientific Reports 2020, 10: 3213. PMID: 32081855, PMCID: PMC7035262, DOI: 10.1038/s41598-020-60028-z.Peer-Reviewed Original ResearchConceptsMaximum electroshock-induced seizuresEpilepsy of infancyPentylenetetrazole-induced seizuresVideo-EEG monitoringElectroshock-induced seizuresForms of epilepsyWild-type miceSlack channelsImpaired motor skillsProcedural motor learningMotor skillsWild-type animalsSevere intellectual disabilityOpen-field behaviorCortical seizuresKCNT1 geneSpontaneous seizuresFocal seizuresSeizure susceptibilitySeizure activityType miceMouse modelAnimal modelsInterictal spikesSeizures
2019
Phactr1 regulates Slack (KCNT1) channels via protein phosphatase 1 (PP1)
Ali SR, Malone TJ, Zhang Y, Prechova M, Kaczmarek LK. Phactr1 regulates Slack (KCNT1) channels via protein phosphatase 1 (PP1). The FASEB Journal 2019, 34: 1591-1601. PMID: 31914597, PMCID: PMC6956700, DOI: 10.1096/fj.201902366r.Peer-Reviewed Original ResearchConceptsProtein phosphatase 1Phosphatase 1Binding of PP1C-terminusCytoplasmic signaling proteinsCytoplasmic C-terminusActin-binding proteinsSlack channelsPKC phosphorylation sitesPhosphoprotein substratesDisease-causing mutationsPhosphorylation sitesSignaling proteinsSlack currentsHuman mutationsSodium-activated potassium channelsPHACTR1Slack genePotassium channelsProteinActinMutationsPatch-clamp recordingsCentral nervous systemMutants
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
2014
Human Slack Potassium Channel Mutations Increase Positive Cooperativity between Individual Channels
Kim GE, Kronengold J, Barcia G, Quraishi IH, Martin HC, Blair E, Taylor JC, Dulac O, Colleaux L, Nabbout R, Kaczmarek LK. Human Slack Potassium Channel Mutations Increase Positive Cooperativity between Individual Channels. Cell Reports 2014, 9: 1661-1672. PMID: 25482562, PMCID: PMC4294418, DOI: 10.1016/j.celrep.2014.11.015.Peer-Reviewed Original ResearchDisrupted in Schizophrenia 1 Modulates Medial Prefrontal Cortex Pyramidal Neuron Activity Through cAMP Regulation of Transient Receptor Potential C and Small-Conductance K+ Channels
El-Hassar L, Simen AA, Duque A, Patel KD, Kaczmarek LK, Arnsten AF, Yeckel MF. Disrupted in Schizophrenia 1 Modulates Medial Prefrontal Cortex Pyramidal Neuron Activity Through cAMP Regulation of Transient Receptor Potential C and Small-Conductance K+ Channels. Biological Psychiatry 2014, 76: 476-485. PMID: 24560582, PMCID: PMC4104266, DOI: 10.1016/j.biopsych.2013.12.019.Peer-Reviewed Original ResearchConceptsCyclic adenosine monophosphateIntracellular Ca2Prefrontal cortical pyramidal neuronsReceptor-mediated intracellular Ca2Regulation of cAMPPrefrontal cortical slicesCortical pyramidal neuronsDISC1 functionMajor depressive disorderPyramidal neuron activityPatch-clamp recordingsTRPC channel activityDISC1 disruptionPrefrontal cortex activityPyramidal neuronsCortical slicesDepressive disorderAdult ratsIntracellular calcium wavesSustained depolarizationViral knockdownNeuron activityBipolar disorderMental disordersCAMP generation
2012
De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy
Barcia G, Fleming MR, Deligniere A, Gazula VR, Brown MR, Langouet M, Chen H, Kronengold J, Abhyankar A, Cilio R, Nitschke P, Kaminska A, Boddaert N, Casanova JL, Desguerre I, Munnich A, Dulac O, Kaczmarek LK, Colleaux L, Nabbout R. De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy. Nature Genetics 2012, 44: 1255-1259. PMID: 23086397, PMCID: PMC3687547, DOI: 10.1038/ng.2441.Peer-Reviewed Original Research
2010
Controlling auditory excitability: the benefits of a cultured environment
Kaczmarek LK. Controlling auditory excitability: the benefits of a cultured environment. The Journal Of Physiology 2010, 588: 1387-1388. PMID: 20436041, PMCID: PMC2876793, DOI: 10.1113/jphysiol.2010.189712.Peer-Reviewed Original ResearchSpecific 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
2009
The N-Terminal Domain of Slack Determines the Formation and Trafficking of Slick/Slack Heteromeric Sodium-Activated Potassium Channels
Chen H, Kronengold J, Yan Y, Gazula VR, Brown MR, Ma L, Ferreira G, Yang Y, Bhattacharjee A, Sigworth FJ, Salkoff L, Kaczmarek LK. The N-Terminal Domain of Slack Determines the Formation and Trafficking of Slick/Slack Heteromeric Sodium-Activated Potassium Channels. Journal Of Neuroscience 2009, 29: 5654-5665. PMID: 19403831, PMCID: PMC3688047, DOI: 10.1523/jneurosci.5978-08.2009.Peer-Reviewed Original ResearchConceptsTerminal domainN-terminal domainAlternative splice variantsPotassium channelsSubcellular localizationPlasma membraneMolecular explanationHeteromer formationSplice variantsHeteromeric channelsDistinct rolesSingle-channel levelSubunitsUnitary conductanceCentral neuronsSlack channelsImmunocytochemical studyFiring patternsDomainLocalizationNeuronsGenesTraffickingChannel levelHomomers
2008
Na+-mediated coupling between AMPA receptors and KNa channels shapes synaptic transmission
Nanou E, Kyriakatos A, Bhattacharjee A, Kaczmarek LK, Paratcha G, Manira A. Na+-mediated coupling between AMPA receptors and KNa channels shapes synaptic transmission. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 20941-20946. PMID: 19095801, PMCID: PMC2634910, DOI: 10.1073/pnas.0806403106.Peer-Reviewed Original ResearchAmino‐termini isoforms of the Slack K+ channel, regulated by alternative promoters, differentially modulate rhythmic firing and adaptation
Brown MR, Kronengold J, Gazula V, Spilianakis CG, Flavell RA, Von Hehn CA, Bhattacharjee A, Kaczmarek LK. Amino‐termini isoforms of the Slack K+ channel, regulated by alternative promoters, differentially modulate rhythmic firing and adaptation. The Journal Of Physiology 2008, 586: 5161-5179. PMID: 18787033, PMCID: PMC2652154, DOI: 10.1113/jphysiol.2008.160861.Peer-Reviewed Original ResearchAction PotentialsAdaptation, PhysiologicalAmino Acid SequenceAnimalsBrainCloning, MolecularGene Expression RegulationMiceMice, Inbred C57BLMolecular Sequence DataNerve Tissue ProteinsNeuronsPotassium ChannelsPotassium Channels, Sodium-ActivatedPromoter Regions, GeneticProtein IsoformsRatsRNA, Messenger
2007
Comparative effects of sodium pyrithione evoked intracellular calcium elevation in rodent and primate ventral horn motor neurons
Knox RJ, Keen KL, Luchansky L, Terasawa E, Freyer H, Barbee SJ, Kaczmarek LK. Comparative effects of sodium pyrithione evoked intracellular calcium elevation in rodent and primate ventral horn motor neurons. Biochemical And Biophysical Research Communications 2007, 366: 48-53. PMID: 18053804, DOI: 10.1016/j.bbrc.2007.11.083.Peer-Reviewed Original ResearchConceptsNeuron-specific enolaseMotor neuronsDose-response curveFura-PE3/AMVentral horn motor neuronsAplysia neuronsSpinal cord slicesIntracellular calcium elevationStore-operated calcium entryCord slicesHindlimb weaknessSpecific enolaseSKF-96365Oral administrationRhesus monkey embryosCalcium entryEffects of NAPCalcium elevationPersistent influxNeuronsMammalian neuronsIslet-1Sodium pyrithioneComparative effectsPlasma membrane
2006
Modulation of Kv3.1b Potassium Channel Phosphorylation in Auditory Neurons by Conventional and Novel Protein Kinase C Isozymes*
Song P, Kaczmarek LK. Modulation of Kv3.1b Potassium Channel Phosphorylation in Auditory Neurons by Conventional and Novel Protein Kinase C Isozymes*. Journal Of Biological Chemistry 2006, 281: 15582-15591. PMID: 16595659, DOI: 10.1074/jbc.m512866200.Peer-Reviewed Original ResearchConceptsAuditory neuronsMNTB neuronsTrapezoid bodyBrief high-frequency electrical stimulationProtein kinase CMetabotropic glutamate receptor activationHigh-frequency electrical stimulationBasal phosphorylationGlutamate receptor activationHigh-frequency stimulationFrequency electrical stimulationHigh-frequency firingMature nervous systemKv3.1 potassium channelNeuronal abilityBrainstem slicesMedial nucleusFrequency stimulationAuditory brainstemFrequency firingConventional protein kinase CPharmacological activationNervous systemElectrical stimulationPKC isozymes
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 CLocalization of the Na+‐activated K+ channel Slick in the rat central nervous system
Bhattacharjee A, von Hehn CA, Mei X, Kaczmarek LK. Localization of the Na+‐activated K+ channel Slick in the rat central nervous system. The Journal Of Comparative Neurology 2005, 484: 80-92. PMID: 15717307, DOI: 10.1002/cne.20462.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAuditory PathwaysCentral Nervous SystemCHO CellsComputer SimulationCricetinaeDNA, ComplementaryFacial NerveImmunoblottingImmunohistochemistryIn Situ HybridizationKineticsModels, NeurologicalNeuronsOlfactory BulbPotassium ChannelsPotassium Channels, Sodium-ActivatedRatsReverse Transcriptase Polymerase Chain ReactionRNA ProbesSubcellular FractionsConceptsRat central nervous systemCentral nervous systemNervous systemAuditory neuronsCortical layers IIHigh-frequency stimulationLow-frequency firingDeep cerebellar nucleiSubstantia nigraTrapezoid bodyVestibular nucleiHippocampal CA1Dentate gyrusMedial nucleusCA3 regionOculomotor nucleusCertain neuronsFacial nucleusNeuronal nucleiOlfactory bulbPontine nucleiImmunohistochemical techniquesRed nucleusLayers IISupraoptic nucleusAminoglycosides block the Kv3.1 potassium channel and reduce the ability of inferior colliculus neurons to fire at high frequencies
Liu S, Kaczmarek LK. Aminoglycosides block the Kv3.1 potassium channel and reduce the ability of inferior colliculus neurons to fire at high frequencies. Developmental Neurobiology 2005, 62: 439-452. PMID: 15547932, DOI: 10.1002/neu.20112.Peer-Reviewed Original ResearchConceptsInferior colliculus neuronsKv3.1 potassium channelColliculus neuronsKv3.1 currentsHearing lossAuditory neuronsPotassium channelsInhibition of Kv3.1Progressive hearing lossRate of repolarizationAuditory nucleiPotassium currentFiring propertiesPipette solutionAction potentialsNeuronsHigh frequencyEffect of streptomycinExtracellular TEAKv3.1 geneKv3.1 channelsAminoglycoside antibioticsStreptomycinKv3.1Presence of streptomycin
2003
Slick (Slo2.1), a Rapidly-Gating Sodium-Activated Potassium Channel Inhibited by ATP
Bhattacharjee A, Joiner WJ, Wu M, Yang Y, Sigworth FJ, Kaczmarek LK. Slick (Slo2.1), a Rapidly-Gating Sodium-Activated Potassium Channel Inhibited by ATP. Journal Of Neuroscience 2003, 23: 11681-11691. PMID: 14684870, PMCID: PMC6740956, DOI: 10.1523/jneurosci.23-37-11681.2003.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAmino Acid SequenceAnimalsCells, CulturedChloridesCHO CellsCloning, MolecularCricetinaeElectric ConductivityHumansIon Channel GatingKineticsMolecular Sequence DataPotassium ChannelsPotassium Channels, Sodium-ActivatedRatsSequence AlignmentSodiumTissue DistributionXenopusModulation of mitochondrial function by endogenous Zn2+ pools
Sensi SL, Ton-That D, Sullivan PG, Jonas EA, Gee KR, Kaczmarek LK, Weiss JH. Modulation of mitochondrial function by endogenous Zn2+ pools. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 6157-6162. PMID: 12724524, PMCID: PMC156342, DOI: 10.1073/pnas.1031598100.Peer-Reviewed Original ResearchConceptsDirect patch-clamp recordingsCultured cortical neuronsPatch-clamp recordingsCertain brain regionsNeuronal injuryPool of intracellularCortical neuronsIntact neuronsReactive oxygen species generationPostsynaptic neuronsClamp recordingsSynaptic spacePotent effectsBrain regionsOxygen species generationBrain mitochondriaMitochondrial poolMembrane depolarizationNeuronsRecent evidenceFurther studiesMitochondrial functionROS generationNovel evidenceSpecies generation
2002
Localization of the Slack potassium channel in the rat central nervous system
Bhattacharjee A, Gan L, Kaczmarek LK. Localization of the Slack potassium channel in the rat central nervous system. The Journal Of Comparative Neurology 2002, 454: 241-254. PMID: 12442315, DOI: 10.1002/cne.10439.Peer-Reviewed Original ResearchConceptsRat central nervous systemSlack potassium channelsChannel subunitsRat brain slicesCentral nervous systemRat brain membranesOnly cortical regionDeep cerebellar nucleiGiant presynaptic terminalSlo subunitWestern blot analysisSubstantia nigraTrigeminal systemImmunohistochemical studyMedial nucleusOculomotor nucleusReticular formationBrain slicesFrontal cortexOlfactory bulbPresynaptic terminalsRed nucleusNervous systemCerebellar nucleiBrain membranesHSV-1 Helper Virus 5dl1.2 Suppresses Sodium Currents in Amplicon-Transduced Neurons
White BH, Cummins TR, Wolf DH, Waxman SG, Russell DS, Kaczmarek LK. HSV-1 Helper Virus 5dl1.2 Suppresses Sodium Currents in Amplicon-Transduced Neurons. Journal Of Neurophysiology 2002, 87: 2149-2157. PMID: 11929932, DOI: 10.1152/jn.00498.2001.Peer-Reviewed Original ResearchConceptsSodium currentAnti-HSV antibodiesAverage spike frequencyWild-type HSV-1Helper virusViral-based strategiesDays of transductionCultured neuronsHSV-1Spike frequencyGene deliveryNeuronsMammalian neuronsAmplicon systemSimilar suppressionHSV-1 genesVirusTherapeutic purposesViral proteinsAmplicon preparationsCellsCoinfectionSuppressionPreparation resultsTiters