2023
Modulation of potassium conductances optimizes fidelity of auditory information
Kaczmarek L. Modulation of potassium conductances optimizes fidelity of auditory information. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2216440120. PMID: 36930599, PMCID: PMC10041146, DOI: 10.1073/pnas.2216440120.Peer-Reviewed Original ResearchConceptsPotassium currentAuditory brainstem neuronsAuditory stimuliHigh-frequency firingGroups of neuronsLow-frequency stimuliBrainstem neuronsHigh-frequency stimuliIntrinsic excitabilityEnsembles of neuronsPostsynaptic neuronsAuditory neuronsNeurotransmitter releaseModulatory mechanismsAuditory stimulationFiring ratePotassium conductanceNeuronsPotassium channelsSingle neuronsAmplitude of currentsLoud soundsEnvironmental sound levelsChannel activityPositive membrane potentials
2021
Modulation of Neuronal Potassium Channels During Auditory Processing
Wu J, Kaczmarek LK. Modulation of Neuronal Potassium Channels During Auditory Processing. Frontiers In Neuroscience 2021, 15: 596478. PMID: 33613177, PMCID: PMC7887315, DOI: 10.3389/fnins.2021.596478.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsPotassium channelsAuditory brainstem neuronsAuditory brainstem nucleiNeuronal potassium channelsAuditory informationBrainstem neuronsBrainstem nucleiCertain neuronsPotassium currentFiring patternsNeuronsGene mutationsAuditory processingAuditory stimuliHigh rateLong-term modulationComplex auditory informationIntrinsic electrical propertiesSuch modulationHuman gene mutationsIntensity of soundAuditory environmentModulation
2019
An 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 cells
2017
An 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
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
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 stimulation
2006
Policing the Ball: A New Potassium Channel Subunit Determines Inactivation Rate
Kaczmarek LK. Policing the Ball: A New Potassium Channel Subunit Determines Inactivation Rate. Neuron 2006, 49: 642-644. PMID: 16504937, DOI: 10.1016/j.neuron.2006.02.011.Peer-Reviewed Original Research
2005
Aminoglycosides 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
2001
Ion Channels, Membrane Ion Currents, and the Action Potential
B.Levitan I, Kaczmarek L. Ion Channels, Membrane Ion Currents, and the Action Potential. 2001, 113-138. DOI: 10.1093/oso/9780195145236.003.0006.Peer-Reviewed Original ResearchIon channelsPotassium channel proteinIon currentDetailed mechanistic understandingMembrane proteinsMolecular detailsActive ion channelsChannel proteinsBiological membranesMechanistic understandingSingle-channel recordingsProteinMembrane ion currentsVoltage-clamp measurementsMembraneChannel recordingsCellsMacroscopic currentsClamp measurementsCurrentElectrical phenomenaVoltage clampCurrent chapterMacroscopic membranesPotassium currentDiversity in the Structure and Function of Ion Channels
B.Levitan I, Kaczmarek L. Diversity in the Structure and Function of Ion Channels. 2001, 139-162. DOI: 10.1093/oso/9780195145236.003.0007.Peer-Reviewed Original ResearchIon channelsGreat diversityDiversityConsiderable diversityRapid membrane depolarizationMembrane depolarizationElectrical activityVoltage-dependent sodium currentsVoltage-dependent potassium currentsAxonal membraneSquid giant axonNeuronal cell bodiesCell bodiesGiant axonsPotassium currentAction potentialsSodium currentMembraneActivityAxons
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
1999
Shaw‐like potassium currents in the auditory rhombencephalon throughout embryogenesis
Hendriks R, Morest D, Kaczmarek L. Shaw‐like potassium currents in the auditory rhombencephalon throughout embryogenesis. Journal Of Neuroscience Research 1999, 58: 791-804. PMID: 10583910, DOI: 10.1002/(sici)1097-4547(19991215)58:6<791::aid-jnr6>3.0.co;2-3.Peer-Reviewed Original ResearchConceptsPotassium currentNucleus magnocellularisOutward currentsWhole-cell patch recordingsInitial transient componentTransient outward currentsEarly neuronal developmentEarly neuronal differentiationHigh activation thresholdFirst synapsesAuditory nucleiPatch recordingsPotassium channel genesSynaptic functionCharacteristic response propertiesSynapses formNeuronal developmentNeuronal differentiationActivation thresholdDevelopmental appearanceTetraethylammoniumMagnocellularisEarly ageChannel genesNeuroblastsRole in neuronal cell migration for high‐threshold potassium currents in the chicken hindbrain
Hendriks R, Morest D, Kaczmarek L. Role in neuronal cell migration for high‐threshold potassium currents in the chicken hindbrain. Journal Of Neuroscience Research 1999, 58: 805-814. PMID: 10583911, DOI: 10.1002/(sici)1097-4547(19991215)58:6<805::aid-jnr7>3.0.co;2-v.Peer-Reviewed Original ResearchConceptsChannel blockersPotassium currentWhole-cell patch-clamp recordingsPotassium conductanceN-type calcium channelsPotassium channelsHigh-threshold potassium currentsCalcium channel blockersSensitive potassium channelsPotassium channel blockerPatch-clamp recordingsTetraethylammonium chlorideChronic blockadeNovel potassium channelNeuronal cell migrationTEA exposureCalcium channelsClamp recordingsEmbryonic neuronsSynaptic functionOutward currentsNeuronal migrationElectrical excitabilityMigratory activityIndividual neuroblasts
1998
Depolarization Selectively Increases the Expression of the Kv3.1 Potassium Channel in Developing Inferior Colliculus Neurons
Liu S, Kaczmarek L. Depolarization Selectively Increases the Expression of the Kv3.1 Potassium Channel in Developing Inferior Colliculus Neurons. Journal Of Neuroscience 1998, 18: 8758-8769. PMID: 9786983, PMCID: PMC6793528, DOI: 10.1523/jneurosci.18-21-08758.1998.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsAnimals, NewbornCalciumGene Expression Regulation, DevelopmentalIn Vitro TechniquesInferior ColliculiMembrane PotentialsNeuropeptidesPatch-Clamp TechniquesPotassiumPotassium ChannelsPotassium Channels, Voltage-GatedRatsRats, Sprague-DawleyRNA, MessengerShaw Potassium ChannelsConceptsInferior colliculus neuronsOnset of hearingColliculus neuronsCalcium influxChannel subunitsPotassium currentAction potentialsElevated external potassium concentrationCalcium channel blockersDepolarization-induced increaseSpontaneous neuronal activityNoninactivating potassium currentKv3.1 potassium channelVoltage-clamp experimentsChannel blockersNeuronal excitabilityElevated potassiumAuditory neuronsNeuronal activityExternal potassium concentrationExternal potassium ionsNeuronsPotassium channelsMRNA levelsMarked increaseWhen, where, and how much? Expression of the Kv3.1 potassium channel in high‐frequency firing neurons
Gan L, Kaczmarek L. When, where, and how much? Expression of the Kv3.1 potassium channel in high‐frequency firing neurons. Developmental Neurobiology 1998, 37: 69-79. PMID: 9777733, DOI: 10.1002/(sici)1097-4695(199810)37:1<69::aid-neu6>3.0.co;2-6.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAuditory brain stem neuronsVoltage-dependent potassium currentsBrain stem neuronsHigh-frequency firing neuronsKv3.1 potassium channelStem neuronsKv3.1 potassium channel geneLong-term regulationSynaptic inputsPotassium currentPotassium channel genesNeuronsPotassium channelsKv3.1 geneKv3.1 subunitsFiring neuronsHigh frequencyChannel genesCurrent knowledgeChannels altersTranscriptional mechanismsCell-type specificityExpressionGene transcriptionExtrinsic factors
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
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
Expression of the H-ras oncogene induces potassium conductance and neuron-specific potassium channel mRNAs in the AtT20 cell line
Hemmick L, Perney T, Flamm R, Kaczmarek L, Birnberg N. Expression of the H-ras oncogene induces potassium conductance and neuron-specific potassium channel mRNAs in the AtT20 cell line. Journal Of Neuroscience 1992, 12: 2007-2014. PMID: 1607925, PMCID: PMC6575920, DOI: 10.1523/jneurosci.12-06-02007.1992.Peer-Reviewed Original ResearchConceptsRas-transfected cellsAtT20 cell lineAtT20 cellsEJ-ras oncogeneCell linesPotassium channelsVoltage-dependent potassium channelsRas proteinsPituitary-derived cellsMRNA speciesPlasma membraneSpliced productsPotassium channel mRNASame geneChannel mRNADifferential expressionPotassium currentExcitable cellsVoltage-dependent potassium currentsTwo- to threefold increaseMRNAOncogeneSpeciesExpressionPhenotype