2021
Cerebellar Kv3.3 potassium channels activate TANK-binding kinase 1 to regulate trafficking of the cell survival protein Hax-1
Zhang Y, Varela L, Szigeti-Buck K, Williams A, Stoiljkovic M, Šestan-Peša M, Henao-Mejia J, D’Acunzo P, Levy E, Flavell RA, Horvath TL, Kaczmarek LK. Cerebellar Kv3.3 potassium channels activate TANK-binding kinase 1 to regulate trafficking of the cell survival protein Hax-1. Nature Communications 2021, 12: 1731. PMID: 33741962, PMCID: PMC7979925, DOI: 10.1038/s41467-021-22003-8.Peer-Reviewed Original ResearchConceptsTank Binding Kinase 1HAX-1Kv3.3 potassium channelMultivesicular bodiesKinase 1TANK-binding kinase 1Activation of caspasesAnti-apoptotic proteinsPotassium channelsMembrane proteinsBiochemical pathwaysCerebellar neuronsChannels bindCell deathTBK1 activityIon channelsMutant channelsCellular constituentsTraffickingKv3.3 channelsProteinNeuronal survivalMutationsChannel inactivationCaspases
2019
Modulators 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
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
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
2006
Functional analysis of a novel potassium channel (KCNA1) mutation in hereditary myokymia
Chen H, von Hehn C, Kaczmarek LK, Ment LR, Pober BR, Hisama FM. Functional analysis of a novel potassium channel (KCNA1) mutation in hereditary myokymia. Neurogenetics 2006, 8: 131-135. PMID: 17136396, PMCID: PMC1820748, DOI: 10.1007/s10048-006-0071-z.Peer-Reviewed Original ResearchConceptsEpisodic ataxiaAdditional clinical featuresAbsence of epilepsyPotassium channel mutationsVoltage-gated potassium channelsPotassium channel gene KCNA1Febrile illnessCerebral palsyClinical featuresExtensor plantarsNonconservative missense mutationElectrophysiological studiesVermiform movementsKv1.1 subunitsLoss of functionMotor delayMyokymiaAutosomal dominant traitPotassium channelsChannel mutationsNovel c.AtaxiaMutation analysisMissense mutationsMutant cRNA
2003
Compensatory Anion Currents in Kv1.3 Channel-deficient Thymocytes*
Koni PA, Khanna R, Chang MC, Tang MD, Kaczmarek LK, Schlichter LC, Flavell R. Compensatory Anion Currents in Kv1.3 Channel-deficient Thymocytes*. Journal Of Biological Chemistry 2003, 278: 39443-39451. PMID: 12878608, DOI: 10.1074/jbc.m304879200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBase SequenceCell DivisionChloride ChannelsDNAFemaleGene ExpressionIon TransportKv1.3 Potassium ChannelLymphocyte ActivationMaleMembrane PotentialsMiceMice, Inbred C57BLMice, KnockoutPatch-Clamp TechniquesPotassium ChannelsPotassium Channels, Voltage-GatedRNA, MessengerT-LymphocytesConceptsWild-type cellsKv1.3-/- micePotassium channel subunitsVoltage-gated potassium channelsMouse thymocyte subsetsChloride currentsChannel subunitsAnion currentsT-cell activation/proliferationVoltage-dependent potassium currentsVolume regulationCell proliferationThymocyte apoptosisT cell responsesCell-mediated cytotoxicityObvious defectsCell activation/proliferationImmune system defectsT cell proliferationActivation/proliferationPotassium channelsLymph nodesCompensatory effectLymphocyte typeKv1.3The Sodium-Activated Potassium Channel Is Encoded by a Member of the Slo Gene Family
Yuan A, Santi CM, Wei A, Wang Z, Pollak K, Nonet M, Kaczmarek L, Crowder CM, Salkoff L. The Sodium-Activated Potassium Channel Is Encoded by a Member of the Slo Gene Family. Neuron 2003, 37: 765-773. PMID: 12628167, DOI: 10.1016/s0896-6273(03)00096-5.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCaenorhabditis elegansCells, CulturedFemaleLarge-Conductance Calcium-Activated Potassium ChannelsMembrane PotentialsMolecular Sequence DataMultigene FamilyMutationNerve Tissue ProteinsOocytesPotassium ChannelsPotassium Channels, Calcium-ActivatedPotassium Channels, Sodium-ActivatedSequence Homology, Amino AcidSodiumXenopus
2002
Endogenous parathyroid hormone-related protein functions as a neuroprotective agent
Chatterjee O, Nakchbandi IA, Philbrick WM, Dreyer BE, Zhang J, Kaczmarek LK, Brines ML, Broadus AE. Endogenous parathyroid hormone-related protein functions as a neuroprotective agent. Brain Research 2002, 930: 58-66. PMID: 11879796, DOI: 10.1016/s0006-8993(01)03407-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain NeoplasmsCalcium ChannelsCells, CulturedCerebral CortexDose-Response Relationship, DrugExcitatory Amino Acid AgonistsFemaleInjections, IntraperitonealKainic AcidL-Lactate DehydrogenaseMiceMice, KnockoutNeuroblastomaNeuronsNeuroprotective AgentsParathyroid Hormone-Related ProteinPatch-Clamp TechniquesPregnancyProteinsConceptsL-type voltage-sensitive calcium channelsCalcium channelsHippocampal c-Fos expressionVoltage-sensitive calcium channelsKainic acid-induced excitotoxicityCerebral cortical culturesFunction of PTHrPKainic acid excitotoxicityL-type calcium channelsCultured cerebellar granule cellsSensitive calcium channelsHormone-related proteinCentral nervous systemWhole-cell techniqueC-fos expressionCultured mouse neuroblastoma cellsCerebellar granule cellsMouse neuroblastoma cellsKainate toxicityCerebral cortexNeuroprotective agentsKainic acidLittermate miceCortical culturesPTHrP functions
2001
Targeted Attenuation of Electrical Activity in Drosophila Using a Genetically Modified K+ Channel
White B, Osterwalder T, Yoon K, Joiner W, Whim M, Kaczmarek L, Keshishian H. Targeted Attenuation of Electrical Activity in Drosophila Using a Genetically Modified K+ Channel. Neuron 2001, 31: 699-711. PMID: 11567611, DOI: 10.1016/s0896-6273(01)00415-9.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAnimalsBehavior, AnimalCells, CulturedDrosophila melanogasterDrosophila ProteinsFemaleGene DosageGene Expression Regulation, DevelopmentalGene TargetingGenes, LethalLarvaMembrane PotentialsMusclesMutationNervous SystemNeural InhibitionNeuronsNeurons, AfferentPhenotypePhotoreceptor Cells, InvertebratePotassium ChannelsShaker Superfamily of Potassium ChannelsSynaptic TransmissionTransgenesLocalization of two high‐threshold potassium channel subunits in the rat central auditory system
Li W, Kaczmarek L, Perney T. Localization of two high‐threshold potassium channel subunits in the rat central auditory system. The Journal Of Comparative Neurology 2001, 437: 196-218. PMID: 11494252, DOI: 10.1002/cne.1279.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAuditory PathwaysCochlear NucleusFemaleGene ExpressionGeniculate BodiesImmunohistochemistryIn Situ HybridizationInferior ColliculiNeuronsNeuropeptidesOligonucleotide ProbesOlivary NucleusPotassium ChannelsPotassium Channels, Voltage-GatedRatsRats, Sprague-DawleyRNA, MessengerShaw Potassium ChannelsConceptsAuditory neuronsKv3.1 mRNAPotassium channelsMost auditory neuronsBrainstem auditory neuronsRat central auditory systemAction potential thresholdSubpopulation of neuronsCentral auditory systemLateral superior oliveRat auditory systemAuditory systemVoltage-sensitive potassium channelsRapid deactivation kineticsPotassium channel subunitsTrapezoid bodyRat brainstemMedial nucleusVentral nucleusLateral lemniscusTerminal arborizationsSynaptic inputsAuditory nucleiSuperior oliveChannel expression
2000
Modification of delayed rectifier potassium currents by the Kv9.1 potassium channel subunit
Richardson F, Kaczmarek L. Modification of delayed rectifier potassium currents by the Kv9.1 potassium channel subunit. Hearing Research 2000, 147: 21-30. PMID: 10962170, DOI: 10.1016/s0378-5955(00)00117-9.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAuditory PathwaysComputer SimulationDelayed Rectifier Potassium ChannelsEvoked Potentials, AuditoryFemaleHumansIn Vitro TechniquesMembrane PotentialsModels, NeurologicalNeuronsOocytesPotassium ChannelsPotassium Channels, Voltage-GatedRatsRecombinant ProteinsShab Potassium ChannelsXenopus laevisConceptsRectifier potassium currentPotassium channel subunitsChannel subunitsPotassium currentInward currentsInhibition of firingHigh-frequency stimulationVariety of neuronsPotassium channel alpha subunitChannel alpha subunitFrequency stimulationAuditory pathwayInferior colliculusSustained depolarizationAction potentialsModel neuronsFiring patternsKv9.1NeuronsPotassium channelsAmplitude of currentsKv2.1Sound stimuliRate of activationTetraethyl ammonium ions
1998
Activation of Kv3.1 channels in neuronal spine-like structures may induce local potassium ion depletion
Wang L, Gan L, Perney T, Schwartz I, Kaczmarek L. Activation of Kv3.1 channels in neuronal spine-like structures may induce local potassium ion depletion. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 1882-1887. PMID: 9465111, PMCID: PMC19207, DOI: 10.1073/pnas.95.4.1882.Peer-Reviewed Original ResearchConceptsSpine-like structuresIon channelsMembrane structureMembrane compartmentsVesicle compartmentKv3.1 channelsBulk cytoplasmElectron immunomicroscopyCHO cellsPostsynaptic membraneVesiclesMembrane patchesSpine-like protrusionsNeuronal membrane structurePotassium channel Kv3.1Channel Kv3.1CellsComplete inactivationInactivationCompartmentsRapid depletionCentral nervous systemSlow refillingSynaptic stimulationNeuronal structures
1997
Properties and regulation of the minK potassium channel protein
Kaczmarek L, Blumenthal E. Properties and regulation of the minK potassium channel protein. Physiological Reviews 1997, 77: 627-641. PMID: 9234960, DOI: 10.1152/physrev.1997.77.3.627.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMinK proteinSingle transmembrane segmentPotassium channel proteinChannel-forming subunitTransmembrane segmentsMink genesChannel proteinsSecond messengerAmino acidsKvLQT1 channelsXenopus oocytesProteinNative currentsEpithelial cellsMinK mRNAIon selectivityVoltage-dependent potassium currentsResultant channelPotassium currentStrong candidateCellsGenesSubunitsVestibular organsMessenger
1994
Cyclic AMP modulates fast axonal transport in aplysia bag cell neurons by increasing the probability of single organelle movement
Azhderian EM, Hefner D, Lin C, Kaczmarek LK, Forscher P. Cyclic AMP modulates fast axonal transport in aplysia bag cell neurons by increasing the probability of single organelle movement. Neuron 1994, 12: 1223-1233. PMID: 7516686, DOI: 10.1016/0896-6273(94)90439-1.Peer-Reviewed Original ResearchA shab potassium channel contributes to action potential broadening in peptidergic neurons
Quattrocki E, Marshall J, Kaczmarek L. A shab potassium channel contributes to action potential broadening in peptidergic neurons. Neuron 1994, 12: 73-86. PMID: 8292361, DOI: 10.1016/0896-6273(94)90153-8.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAmino Acid SequenceAnimalsAplysiaBase SequenceCloning, MolecularDNA, ComplementaryFemaleInvertebrate HormonesKineticsMathematicsModels, TheoreticalMolecular Sequence DataNeuronsOocytesPolymerase Chain ReactionPotassiumPotassium ChannelsShab Potassium ChannelsTetraethylammoniumTetraethylammonium CompoundsTranscription, GeneticXenopus laevis
1993
Inward rectification of the minK potassium channel
Blumenthal E, Kaczmarek L. Inward rectification of the minK potassium channel. The Journal Of Membrane Biology 1993, 136: 23-29. PMID: 8271270, DOI: 10.1007/bf00241486.Peer-Reviewed Original Research
1992
Modulation by cAMP of a slowly activating potassium channel expressed in Xenopus oocytes
Blumenthal E, Kaczmarek L. Modulation by cAMP of a slowly activating potassium channel expressed in Xenopus oocytes. Journal Of Neuroscience 1992, 12: 290-296. PMID: 1370322, PMCID: PMC6575684, DOI: 10.1523/jneurosci.12-01-00290.1992.Peer-Reviewed Original ResearchMeSH Keywords8-Bromo Cyclic Adenosine MonophosphateAmino Acid SequenceAnimalsCell MembraneCyclic AMPFemaleGene ExpressionHumansMembrane PotentialsMembrane ProteinsMolecular Sequence DataMutagenesis, Site-DirectedOocytesPhosphorylationPotassium ChannelsPotassium Channels, Voltage-GatedProgesteroneProtein Kinase InhibitorsProtein KinasesRatsRNATransfectionXenopus laevisConceptsMinK proteinCAMP-dependent protein kinasePotential phosphorylation sitesXenopus oocytesCAMP levelsPhosphorylation sitesProtein kinasePlasma membraneKinase activityChannel proteinsIntracellular cAMP levelsProtein inhibitorProteinKinasePotassium channelsOocytesVoltage-dependent potassium currentsIsK
1990
Cloning and expression of cDNA and genomic clones encoding three delayed rectifier potassium channels in rat brain
Swanson R, Marshall J, Smith J, Williams J, Boyle M, Folander K, Luneau C, Antanavage J, Oliva C, Buhrow S, Bennet C, Stein R, Kaczmarek L. Cloning and expression of cDNA and genomic clones encoding three delayed rectifier potassium channels in rat brain. Neuron 1990, 4: 929-939. PMID: 2361015, DOI: 10.1016/0896-6273(90)90146-7.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceBrainCloning, MolecularDNAFemaleMembrane ProteinsMolecular Sequence DataOligonucleotide ProbesOocytesOrgan SpecificityPotassium ChannelsProtein BiosynthesisRatsRats, Inbred StrainsRestriction MappingRNA, MessengerSequence Homology, Nucleic AcidTranscription, GeneticXenopusEstrogen induction of a small, putative K+ channel mRNA in rat uterus
Pragnell M, Snay K, Trimmer J, MacLusky N, Naftolin F, Kaczmarek L, Boyle M. Estrogen induction of a small, putative K+ channel mRNA in rat uterus. Neuron 1990, 4: 807-812. PMID: 2344412, DOI: 10.1016/0896-6273(90)90207-v.Peer-Reviewed Original ResearchConceptsMRNA speciesAmino acid proteinProkaryotic ion channelsDramatic long-term changesMolecular cloningAcid proteinIon channel expressionMammalian sourcesIon channelsXenopus oocytesVoltage-dependent channelsSpeciesStructural motifsCritical roleChannel expressionMRNAChannel mRNAEstrogen inductionLong-term changesInductionCloningProteinMotifRegulationOocytes