2021
A KCNC1 mutation in epilepsy of infancy with focal migrating seizures produces functional channels that fail to be regulated by PKC phosphorylation
Zhang Y, Ali SR, Nabbout R, Barcia G, Kaczmarek LK. A KCNC1 mutation in epilepsy of infancy with focal migrating seizures produces functional channels that fail to be regulated by PKC phosphorylation. Journal Of Neurophysiology 2021, 126: 532-539. PMID: 34232791, PMCID: PMC8409950, DOI: 10.1152/jn.00257.2021.Peer-Reviewed Original ResearchConceptsFunctional channelsProtein kinase C.Serious human diseasesPotassium channelsWild-type channelsEpilepsy of infancyChannel modulationTerminal domainIon channel mutationsPKC phosphorylationC-terminusNormal neuronal functionChannel proteinsKv3.1 potassium channelRegulatory sitesKinase C.Human diseasesChannel functionPhosphorylationIon channelsMutationsNovo variantsChannel mutationsBiophysical propertiesNeuronal functionPresynaptic Kv3 channels are required for fast and slow endocytosis of synaptic vesicles
Wu XS, Subramanian S, Zhang Y, Shi B, Xia J, Li T, Guo X, El-Hassar L, Szigeti-Buck K, Henao-Mejia J, Flavell RA, Horvath TL, Jonas EA, Kaczmarek LK, Wu LG. Presynaptic Kv3 channels are required for fast and slow endocytosis of synaptic vesicles. Neuron 2021, 109: 938-946.e5. PMID: 33508244, PMCID: PMC7979485, DOI: 10.1016/j.neuron.2021.01.006.Peer-Reviewed Original ResearchConceptsSlow endocytosisVesicle mobilizationF-actin cytoskeletonChannel mutationsPotassium channelsKv3.3 proteinsInhibits endocytosisRapid endocytosisNovel functionF-actinEndocytosisCrucial functionSynaptic vesiclesFamily channelsSynaptic transmissionDiscovery decadesMembrane potentialNeurotransmitter releaseDiverse neurological disordersIon conductanceMutationsReleasable poolMouse nerve terminalsPotassium channel mutationsPathological effects
2018
C-terminal proline deletions in KCNC3 cause delayed channel inactivation and an adult-onset progressive SCA13 with spasticity
Khare S, Galeano K, Zhang Y, Nick JA, Nick HS, Subramony SH, Sampson J, Kaczmarek LK, Waters MF. C-terminal proline deletions in KCNC3 cause delayed channel inactivation and an adult-onset progressive SCA13 with spasticity. The Cerebellum 2018, 17: 692-697. PMID: 29949095, PMCID: PMC8299775, DOI: 10.1007/s12311-018-0950-5.Peer-Reviewed Original ResearchConceptsIon channel functionMammalian cell cultureMutant proteinsIntracellular cSpinocerebellar ataxia 13Autosomal dominant neurological diseaseChannel functionAllelic heterogeneityProline deletionSCA13 patientsTerminal portionProgressive clinical symptomsNormal membranesCell culturesProteinElectrophysiological characterizationChannel inactivationInactivationClinical symptomsElectrophysiological profileNeurological diseasesClinical importanceSCA13Slow inactivationDeletion
2017
A KCNC3 mutation causes a neurodevelopmental, non-progressive SCA13 subtype associated with dominant negative effects and aberrant EGFR trafficking
Khare S, Nick JA, Zhang Y, Galeano K, Butler B, Khoshbouei H, Rayaprolu S, Hathorn T, Ranum LPW, Smithson L, Golde TE, Paucar M, Morse R, Raff M, Simon J, Nordenskjöld M, Wirdefeldt K, Rincon-Limas DE, Lewis J, Kaczmarek LK, Fernandez-Funez P, Nick HS, Waters MF. A KCNC3 mutation causes a neurodevelopmental, non-progressive SCA13 subtype associated with dominant negative effects and aberrant EGFR trafficking. PLOS ONE 2017, 12: e0173565. PMID: 28467418, PMCID: PMC5414954, DOI: 10.1371/journal.pone.0173565.Peer-Reviewed Original ResearchConceptsDominant negative effectEpidermal growth factor receptorGrowth factor receptorDrosophila epidermal growth factor receptorCongenital onsetPlasma membrane targetingMammalian cells resultsWild-type proteinHuman epidermal growth factor receptorFactor receptorMotor neuron pathologyDominant inheritanceSpinocerebellar ataxiaMembrane targetingEGFR traffickingAberrant retentionEye phenotypeMammalian cellsMammalian systemsVoltage-gated potassium channel KCNC3Autonomic dysfunctionEndosomal vesiclesNeuron pathologyCompensatory neural mechanismsPsychiatric manifestations
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
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 disability
2008
Protein Kinase C Modulates Inactivation of Kv3.3 Channels*
Desai R, Kronengold J, Mei J, Forman SA, Kaczmarek LK. Protein Kinase C Modulates Inactivation of Kv3.3 Channels*. Journal Of Biological Chemistry 2008, 283: 22283-22294. PMID: 18539595, PMCID: PMC2494927, DOI: 10.1074/jbc.m801663200.Peer-Reviewed Original ResearchRepetitive 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
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
2004
The Appearance of a Protein Kinase A-regulated Splice Isoform of slo Is Associated with the Maturation of Neurons That Control Reproductive Behavior*
Zhang Y, Joiner WJ, Bhattacharjee A, Rassendren F, Magoski NS, Kaczmarek LK. The Appearance of a Protein Kinase A-regulated Splice Isoform of slo Is Associated with the Maturation of Neurons That Control Reproductive Behavior*. Journal Of Biological Chemistry 2004, 279: 52324-52330. PMID: 15375169, DOI: 10.1074/jbc.m408543200.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAmino Acid SequenceAnimalsAplysiaCell DifferentiationCHO CellsCricetinaeCyclic AMP-Dependent Protein KinasesDNA, ComplementaryIn Vitro TechniquesLarge-Conductance Calcium-Activated Potassium ChannelsMolecular Sequence DataNeuronsPatch-Clamp TechniquesPotassium Channels, Calcium-ActivatedProtein IsoformsRecombinant ProteinsReproductionConceptsBag cell neuronsReproductive behaviorSlo geneConsensus phosphorylation sitesCell cDNA libraryProtein kinase ACell neuronsChinese hamster ovary cellsPhosphorylation sitesCatalytic subunitHamster ovary cellsAlternative transcriptsCDNA librarySplice isoformsKinase ABK channel activityMaturation of neuronsPKA inhibitorVoltage-dependent channelsOvary cellsBrief synaptic stimulationChannel activityMature neuronsIsoformsPKA
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 the Kv3.1b Potassium Channel Isoform Adjusts the Fidelity of the Firing Pattern of Auditory Neurons
Macica CM, von Hehn CA, Wang LY, Ho CS, Yokoyama S, Joho RH, Kaczmarek LK. Modulation of the Kv3.1b Potassium Channel Isoform Adjusts the Fidelity of the Firing Pattern of Auditory Neurons. Journal Of Neuroscience 2003, 23: 1133-1141. PMID: 12598601, PMCID: PMC6742259, DOI: 10.1523/jneurosci.23-04-01133.2003.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsBrain StemCells, CulturedCHO CellsCricetinaeElectric ConductivityEvoked Potentials, AuditoryKineticsMiceMice, KnockoutNeuronsNeuropeptidesPatch-Clamp TechniquesPhosphorylationPotassium ChannelsPotassium Channels, Voltage-GatedProtein IsoformsProtein Kinase CSerineShaw Potassium ChannelsTetradecanoylphorbol AcetateConceptsTrapezoid bodyMedial nucleusAuditory neuronsHigh-frequency stimulationWild-type neuronsKv3.1 potassium channelHigh-threshold componentPotassium channel isoformsGreat temporal precisionPartial decreaseProtein kinase C activationAction potentialsLocation of soundsMice resultsFiring patternsNeuronsSensory stimulationPotassium channelsChannel isoformsKinase C activationKv3.1Kv3.1 geneStimulationHigh frequencyProtein kinase C
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 membranes
2001
Calmodulin Regulates Assembly and Trafficking of SK4/IK1 Ca2+-activated K+ Channels*
Joiner W, Khanna R, Schlichter L, Kaczmarek L. Calmodulin Regulates Assembly and Trafficking of SK4/IK1 Ca2+-activated K+ Channels*. Journal Of Biological Chemistry 2001, 276: 37980-37985. PMID: 11495911, DOI: 10.1074/jbc.m104965200.Peer-Reviewed Original ResearchConceptsChannel assemblyC-terminusAssembly of channelsIon channelsC-terminal domainDistal C-terminal domainCo-immunoprecipitation experimentsCaM-binding domainSurface expressionDominant negative effectProximal C-terminusWhole-cell currentsCellular functionsCaM genesPlasma membraneCaM proteinFree CaMNovel mechanismTraffickingProteinTerminusAssemblyExpressionSK4DomainCasein Kinase 2 Determines the Voltage Dependence of the Kv3.1 Channel in Auditory Neurons and Transfected Cells
Macica C, Kaczmarek L. Casein Kinase 2 Determines the Voltage Dependence of the Kv3.1 Channel in Auditory Neurons and Transfected Cells. Journal Of Neuroscience 2001, 21: 1160-1168. PMID: 11160386, PMCID: PMC6762230, DOI: 10.1523/jneurosci.21-04-01160.2001.Peer-Reviewed Original ResearchMeSH KeywordsAlkaline PhosphataseAnimalsAuditory PathwaysBinding SitesBrain StemCasein Kinase IICDC2-CDC28 KinasesCHO CellsCricetinaeCyclin-Dependent Kinase 2Cyclin-Dependent KinasesElectric StimulationEnzyme InhibitorsIn Vitro TechniquesMembrane PotentialsNeuronsNeuropeptidesPatch-Clamp TechniquesPhosphorylationPotassium ChannelsPotassium Channels, Voltage-GatedPrecipitin TestsProtein Kinase CProtein Serine-Threonine KinasesRatsShaw Potassium ChannelsTetradecanoylphorbol AcetateTransfectionConceptsCasein kinase 2Kinase 2Casein kinase IIProtein kinase CKv3.1 channelsChinese hamster ovary cellsHamster ovary cellsConstitutive phosphorylationPhosphatase treatmentKinase IIKinase CTransfected CellsVoltage-dependent activationOvary cellsWhole-cell conductancePhosphorylationPotassium channelsRectifier channelsBiophysical characteristicsInactivationKv3.1 potassium channelVoltage dependenceActivationKv3.1Patch-clamp recordings
1999
Cell Type‐Specific Expression of the Kv3.1 Gene Is Mediated by a Negative Element in the 5′ Untranslated Region of the Kv3.1 Promoter
Gan L, Hahn S, Kaczmarek L. Cell Type‐Specific Expression of the Kv3.1 Gene Is Mediated by a Negative Element in the 5′ Untranslated Region of the Kv3.1 Promoter. Journal Of Neurochemistry 1999, 73: 1350-1362. PMID: 10501178, DOI: 10.1046/j.1471-4159.1999.0731350.x.Peer-Reviewed Original ResearchMeSH Keywords3T3 Cells5' Untranslated RegionsAnimalsBase SequenceBeta-GalactosidaseBrainCell LineCHO CellsCloning, MolecularCricetinaeGene Expression RegulationGliomaHumansMiceMice, TransgenicMolecular Sequence DataNeuropeptidesOrgan SpecificityPC12 CellsPotassium ChannelsPotassium Channels, Voltage-GatedPromoter Regions, GeneticRatsRecombinant Fusion ProteinsRegulatory Sequences, Nucleic AcidRNA, MessengerShaw Potassium ChannelsTranscription, GeneticTransfectionConceptsType-specific expressionUntranslated regionCell type-specific enhancersCell type-specific expressionCell linesTissue-specific expressionThymidine kinase promoterCell-type specificityTransient transfection assaysKv3.1 potassium channel genePotassium channel genesKv3.1 geneDifferent tissue originsRegulatory fragmentDeletion analysisRegulatory regionsTranscriptional mechanismsTransgenic miceTransfection assaysKinase promoterFunctional analysisChannel genesType specificityPromoterGeneshSK4/hIK1, a Calmodulin-binding KCa Channel in Human T Lymphocytes ROLES IN PROLIFERATION AND VOLUME REGULATION*
Khanna R, Chang M, Joiner W, Kaczmarek L, Schlichter L. hSK4/hIK1, a Calmodulin-binding KCa Channel in Human T Lymphocytes ROLES IN PROLIFERATION AND VOLUME REGULATION*. Journal Of Biological Chemistry 1999, 274: 14838-14849. PMID: 10329683, DOI: 10.1074/jbc.274.21.14838.Peer-Reviewed Original ResearchConceptsIK currentsActivated T cell functionSecondary immune responseNaive T cellsT cell functionPromising therapeutic targetChinese hamster ovary cellsHamster ovary cellsHuman T lymphocytesVolume regulationKCa channelsT cellsT lymphocytesImmune responseTherapeutic targetIK blockHSK4Accessory moleculesHuman T lymphoblastsOvary cellsDistal C-terminusPharmacological propertiesT lymphoblastsCell functionProximal C-terminus