2021
Suppression of Kv3.3 channels by antisense oligonucleotides reverses biochemical effects and motor impairment in spinocerebellar ataxia type 13 mice
Zhang Y, Quraishi IH, McClure H, Williams LA, Cheng Y, Kale S, Dempsey GT, Agrawal S, Gerber DJ, McManus OB, Kaczmarek LK. Suppression of Kv3.3 channels by antisense oligonucleotides reverses biochemical effects and motor impairment in spinocerebellar ataxia type 13 mice. The FASEB Journal 2021, 35: e22053. PMID: 34820911, PMCID: PMC8630780, DOI: 10.1096/fj.202101356r.Peer-Reviewed Original ResearchConceptsHAX-1Wild-type animalsMultivesicular bodiesKv3.3 channelsLate endosomes/multivesicular bodiesTank Binding Kinase 1Type animalsCell survival proteinsDisease-causing mutationsVoltage-dependent potassium channelsSpinocerebellar ataxia type 13Survival proteinsKinase 1Mature intact animalsTBK1 activationAge-matched wild-type animalsLevels of CD63Progressive cerebellar degenerationWild-type miceMutationsProtein levelsMutant micePotassium channelsDependent potassium channelsType mice
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
2016
Stimulation of Slack K+ Channels Alters Mass at the Plasma Membrane by Triggering Dissociation of a Phosphatase-Regulatory Complex
Fleming MR, Brown MR, Kronengold J, Zhang Y, Jenkins DP, Barcia G, Nabbout R, Bausch AE, Ruth P, Lukowski R, Navaratnam DS, Kaczmarek LK. Stimulation of Slack K+ Channels Alters Mass at the Plasma Membrane by Triggering Dissociation of a Phosphatase-Regulatory Complex. Cell Reports 2016, 16: 2281-2288. PMID: 27545877, PMCID: PMC5123741, DOI: 10.1016/j.celrep.2016.07.024.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsBiosensing TechniquesBithionolBridged Bicyclo Compounds, HeterocyclicCell MembraneCerebral CortexFragile X Mental Retardation ProteinGene Expression RegulationHEK293 CellsHumansIon TransportMiceMice, KnockoutMicrofilament ProteinsMutationNerve Tissue ProteinsNeuronsPatch-Clamp TechniquesPhosphorylationPotassium ChannelsPotassium Channels, Sodium-ActivatedPrimary Cell CultureProtein BindingRNA, Small InterferingSignal TransductionThiazolidinesXenopus laevisConceptsProtein phosphatase 1Plasma membraneProtein kinase C.C-terminal residuesPhactr-1Potassium channelsPhosphatase 1Terminal domainSlack channelsHuman mutationsKinase C.Sodium-activated potassium channelsPharmacological activatorsOptical biosensor assayChannel stimulationSlack currentsBiosensor assaysMembraneMutantsPhosphorylationIntellectual disabilityProteinMutationsSevere intellectual disabilityActivator
2015
The sodium-activated potassium channel Slack is required for optimal cognitive flexibility in mice
Bausch AE, Dieter R, Nann Y, Hausmann M, Meyerdierks N, Kaczmarek LK, Ruth P, Lukowski R. The sodium-activated potassium channel Slack is required for optimal cognitive flexibility in mice. Learning & Memory 2015, 22: 323-335. PMID: 26077685, PMCID: PMC4478330, DOI: 10.1101/lm.037820.114.Peer-Reviewed Original ResearchConceptsFragile X Mental Retardation ProteinCognitive flexibilityFragile X syndromeNormal working memoryAspects of memoryIntellectual disabilityMental retardation proteinSpatial learning capabilitiesSlack channelsWorking memoryBehavioral tasksReference memorySodium-activated potassium channel SlackHigher brain functionsUnfamiliar situationsBrain functionSevere intellectual disabilityMemoryIntellectual developmentSodium-activated potassium channelsNull mouse modelGeneral locomotor activityX syndromeProper functionLearning capabilities
2014
Disrupted 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
2013
Expression of Kv1.3 potassium channels regulates density of cortical interneurons
Duque A, Gazula V, Kaczmarek LK. Expression of Kv1.3 potassium channels regulates density of cortical interneurons. Developmental Neurobiology 2013, 73: 841-855. PMID: 23821603, PMCID: PMC3829632, DOI: 10.1002/dneu.22105.Peer-Reviewed Original ResearchConceptsKv1.3 geneMembrane-spanning channelsKv1.3-/- miceVasoactive intestinal peptideEffect of deletionCerebral cortexKv1.3 potassium channelsNeuropeptide YNeuronal differentiationKv1.3 proteinOlfactory bulbInterneuron populationsSelective poresExpression of Kv1.3Large familyCell membraneKv channelsNumber of calbindinNormal cortical functionWhole cerebral cortexWild-type miceKv1.3GenesDetection of odorsPotassium channels
2011
Bcl-xL regulates mitochondrial energetics by stabilizing the inner membrane potential
Chen YB, Aon MA, Hsu YT, Soane L, Teng X, McCaffery JM, Cheng WC, Qi B, Li H, Alavian KN, Dayhoff-Brannigan M, Zou S, Pineda FJ, O'Rourke B, Ko YH, Pedersen PL, Kaczmarek LK, Jonas EA, Hardwick JM. Bcl-xL regulates mitochondrial energetics by stabilizing the inner membrane potential. Journal Of Cell Biology 2011, 195: 263-276. PMID: 21987637, PMCID: PMC3198165, DOI: 10.1083/jcb.201108059.Peer-Reviewed Original ResearchConceptsMitochondrial membrane potentialMitochondrial membraneMitochondrial ATP synthase β-subunitATP synthase β subunitBcl-2 family proteinsOuter membrane permeabilizationInner mitochondrial membrane potentialMembrane potentialMitochondrial energetic capacityOuter mitochondrial membraneSynthase β subunitInner mitochondrial membraneInner membrane potentialATP synthaseFamily proteinsBiochemical approachesGenetic evidenceEndogenous BclMembrane permeabilizationCellular resourcesΒ-subunitBcl-xLMitochondrial energeticsEnergetic capacityMitochondrial cristae
2010
Fragile X Mental Retardation Protein Is Required for Rapid Experience-Dependent Regulation of the Potassium Channel Kv3.1b
Strumbos JG, Brown MR, Kronengold J, Polley DB, Kaczmarek LK. Fragile X Mental Retardation Protein Is Required for Rapid Experience-Dependent Regulation of the Potassium Channel Kv3.1b. Journal Of Neuroscience 2010, 30: 10263-10271. PMID: 20685971, PMCID: PMC3485078, DOI: 10.1523/jneurosci.1125-10.2010.Peer-Reviewed Original ResearchConceptsMental retardation proteinAnterior ventral cochlear nucleusFragile X Mental Retardation ProteinRNA-binding proteinProtein translationFMRPWild-type animalsSpecific mRNAsSound localization circuitVentral cochlear nucleusBrainstem synaptosomesExperience-dependent regulationProtein levelsAmplitude-modulated stimuliProteinTrapezoid bodyCochlear nucleusMale miceMedial nucleusNeuronal activityPotassium currentWT controlsSynaptic plasticityTonotopic axisAcoustic stimulationLocalization of Kv1.3 channels in presynaptic terminals of brainstem auditory neurons
Gazula V, Strumbos JG, Mei X, Chen H, Rahner C, Kaczmarek LK. Localization of Kv1.3 channels in presynaptic terminals of brainstem auditory neurons. The Journal Of Comparative Neurology 2010, 518: 3205-3220. PMID: 20575068, PMCID: PMC2894291, DOI: 10.1002/cne.22393.Peer-Reviewed Original ResearchConceptsPresynaptic terminalsBrainstem auditory neuronsPattern of stainingMNTB neuronsPrincipal neuronsSynaptic markersTrapezoid bodyCochlear nucleusAfferent inputAxonal stainingMedial nucleusAuditory brainstemPresynaptic endingsOlfactory bulbAuditory neuronsPotassium channel genesTonotopic axisTonotopic gradientNeuronsKv1.3 channelsProminent labelingPrincipal cellsAuditory stimuliKv1 familyKv1.3The Slack Sodium-Activated Potassium Channel Provides a Major Outward Current in Olfactory Neurons of Kv1.3−/− Super-Smeller Mice
Lu S, Das P, Fadool DA, Kaczmarek LK. The Slack Sodium-Activated Potassium Channel Provides a Major Outward Current in Olfactory Neurons of Kv1.3−/− Super-Smeller Mice. Journal Of Neurophysiology 2010, 103: 3311-3319. PMID: 20393063, PMCID: PMC2888249, DOI: 10.1152/jn.00607.2009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBiophysicsCardiovascular AgentsCells, CulturedElectric StimulationGene Expression RegulationIn Vitro TechniquesKv1.3 Potassium ChannelMembrane PotentialsMiceMice, Inbred C57BLMice, KnockoutNerve Tissue ProteinsNeuronsOlfactory BulbPatch-Clamp TechniquesPotassium ChannelsPotassium Channels, Sodium-ActivatedPyrimidinesRNA InterferenceSodium Channel BlockersTetrodotoxinTransfectionConceptsMitral cellsOlfactory bulbOutward currentsOlfactory neuronsWildtype animalsPotassium channelsMajor outward currentVoltage-clamp recordingsVoltage-dependent potassium channelsNet outward currentIntracellular sodiumOB slicesPotassium channel genesCompensatory increaseFiring patternsWestern blottingRNA interference approachPrimary culturesEnhanced expressionDetection of odorsSame treatmentChannel genesMiceNeuronsOlfactory phenotypes
2004
The voltage-gated potassium channel Kv1.3 regulates peripheral insulin sensitivity
Xu J, Wang P, Li Y, Li G, Kaczmarek LK, Wu Y, Koni PA, Flavell RA, Desir GV. The voltage-gated potassium channel Kv1.3 regulates peripheral insulin sensitivity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 3112-3117. PMID: 14981264, PMCID: PMC365752, DOI: 10.1073/pnas.0308450100.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsBiological TransportFastingGlucoseInsulinInterleukin-6JNK Mitogen-Activated Protein KinasesKineticsKv1.3 Potassium ChannelMaleMiceMice, Inbred C57BLMice, KnockoutMice, ObeseMitogen-Activated Protein KinasesModels, BiologicalMuscle, SkeletalPotassium ChannelsPotassium Channels, Voltage-GatedTumor Necrosis Factor-alphaConceptsKv1.3-/- micePeripheral glucose homeostasisPeripheral insulin sensitivityPlasma membraneGene inactivationInsulin sensitivityAmount of GLUT4Skeletal muscleTerminal kinase (JNK) activityGlucose homeostasisAdipose tissueLower blood insulin levelsVoltage-gated potassium channelsInsulin-stimulated glucose uptakeVoltage-gated potassium channel Kv1.3Tumor necrosis factor productionExperimental autoimmune encephalitisBlood insulin levelsHigh-fat dietPotassium channel Kv1.3Tumor necrosis factor secretionPeripheral T lymphocytesKinase activityNecrosis factor productionNumber of tissuesKv1.3 Channel Gene-Targeted Deletion Produces “Super-Smeller Mice” with Altered Glomeruli, Interacting Scaffolding Proteins, and Biophysics
Fadool DA, Tucker K, Perkins R, Fasciani G, Thompson RN, Parsons AD, Overton JM, Koni PA, Flavell RA, Kaczmarek LK. Kv1.3 Channel Gene-Targeted Deletion Produces “Super-Smeller Mice” with Altered Glomeruli, Interacting Scaffolding Proteins, and Biophysics. Neuron 2004, 41: 389-404. PMID: 14766178, PMCID: PMC2737549, DOI: 10.1016/s0896-6273(03)00844-4.Peer-Reviewed Original ResearchMeSH Keywords14-3-3 ProteinsAdaptor Proteins, Vesicular TransportAnimalsBehavior, AnimalBlotting, WesternBody WeightBrain-Derived Neurotrophic FactorCalcium ChannelsCells, CulturedDensitometryDifferential ThresholdDiscrimination, PsychologicalDose-Response Relationship, DrugDrinkingElectric StimulationEmbryo, MammalianEnergy IntakeExploratory BehaviorGene DeletionGRB10 Adaptor ProteinHabituation, PsychophysiologicHumansInsulinKidneyKineticsKv1.3 Potassium ChannelMembrane PotentialsMiceMice, KnockoutMotor ActivityNerve Tissue ProteinsNeuronsNeurotoxinsNuclear Matrix-Associated ProteinsOdorantsOlfactory BulbPatch-Clamp TechniquesPotassium ChannelsPotassium Channels, Voltage-GatedProteinsRas ProteinsReceptor, trkBReverse Transcriptase Polymerase Chain ReactionRNA, MessengerScorpion VenomsSensory ThresholdsSrc-Family KinasesTime FactorsTyrosine 3-MonooxygenaseConceptsKv1.3-/- miceProtein-protein interactionsGene-targeted deletionKv1.3-null miceSignal transductionScaffolding proteinSignaling cascadesChannel genesC-type inactivationDeletionMembrane potentialNull miceOlfactory codingDetection of odorsPotassium channelsKv1.3 channelsProteinSense of smellSlow inactivation kineticsWild-type miceTransductionGenesOlfactory bulb mitral cellsMiceRole
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 typeKv1.3BAK Alters Neuronal Excitability and Can Switch from Anti- to Pro-Death Function during Postnatal Development
Fannjiang Y, Kim CH, Huganir RL, Zou S, Lindsten T, Thompson CB, Mito T, Traystman RJ, Larsen T, Griffin DE, Mandir AS, Dawson TM, Dike S, Sappington AL, Kerr DA, Jonas EA, Kaczmarek LK, Hardwick JM. BAK Alters Neuronal Excitability and Can Switch from Anti- to Pro-Death Function during Postnatal Development. Developmental Cell 2003, 4: 575-585. PMID: 12689595, DOI: 10.1016/s1534-5807(03)00091-1.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnimalsAnimals, NewbornApoptosisBcl-2 Homologous Antagonist-Killer ProteinCentral Nervous SystemCentral Nervous System DiseasesCentral Nervous System Viral DiseasesDisease Models, AnimalEpilepsyExcitatory Postsynaptic PotentialsGenetic VectorsHippocampusKainic AcidMaleMembrane ProteinsMiceMice, KnockoutNeurodegenerative DiseasesNeuronsNeurotoxinsProtein Structure, TertiarySindbis VirusStrokeSynaptic TransmissionConceptsNeuronal excitabilityVirus infectionPostnatal developmentAlters neuronal excitabilityKainate-induced seizuresSpinal cord neuronsIschemia/strokeSindbis virus infectionNeuronal injuryCord neuronsNeuronal deathProtective effectSynaptic activityMouse modelParkinson's diseaseNeuron subtypesNeurotransmitter releasePro-death functionMiceNeuronsSpecific death stimuliDeathSeizuresPossible roleExcitabilityModulation 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
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