2024
Disease-causing Slack potassium channel mutations produce opposite effects on excitability of excitatory and inhibitory neurons
Wu J, Quraishi I, Zhang Y, Bromwich M, Kaczmarek L. Disease-causing Slack potassium channel mutations produce opposite effects on excitability of excitatory and inhibitory neurons. Cell Reports 2024, 43: 113904. PMID: 38457342, PMCID: PMC11013952, DOI: 10.1016/j.celrep.2024.113904.Peer-Reviewed Original ResearchInhibitory neuronsRegulation of neuronal excitabilityPotassium channel mutationsVoltage-dependent sodiumInhibitory cortical neuronsGain-of-function mutationsAxon initial segmentKCNT1 geneNeuronal excitabilityChannel subunitsChannel mutationsNetwork hyperexcitabilityMouse modelNeuron typesCortical neuronsTreat epilepsyNeuronsExcitable neuronsNeurological disordersSevere intellectual disabilityMutationsInitial segmentKCNT1ExpressionHyperexcitability
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
The NaVy paradox: reducing sodium currents increases excitability
Kaczmarek LK. The NaVy paradox: reducing sodium currents increases excitability. Trends In Neurosciences 2021, 44: 767-768. PMID: 34373125, PMCID: PMC8813127, DOI: 10.1016/j.tins.2021.07.008.Peer-Reviewed Original ResearchModulation 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
2020
Excitable Membrane Properties of Neurons
Kaczmarek L. Excitable Membrane Properties of Neurons. 2020, 3-32. DOI: 10.1093/oxfordhb/9780190669164.013.20.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2019
Loss of NaV1.2-Dependent Backpropagating Action Potentials in Dendrites Contributes to Autism and Intellectual Disability
Kaczmarek LK. Loss of NaV1.2-Dependent Backpropagating Action Potentials in Dendrites Contributes to Autism and Intellectual Disability. Neuron 2019, 103: 551-553. PMID: 31437449, DOI: 10.1016/j.neuron.2019.07.032.Peer-Reviewed Original ResearchAn 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
2018
Extraction of Auditory Information by Modulation of Neuronal Ion Channels
Kaczmarek L. Extraction of Auditory Information by Modulation of Neuronal Ion Channels. 2018, 273-300. DOI: 10.1093/oxfordhb/9780190849061.013.23.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsTrapezoid bodyMedial nucleusNeuronal firing patternsGroups of neuronsPotassium channel subunitsAuditory neuronsFiring patternsChannel subunitsAuditory informationIon channelsAuditory inputNeuronal ion channelsSuch modulationComplex soundsSpecific patternsNeuronsIncoming stimuliAuditory environmentIdentical neuronsSame patternVariety of responsesSmall numberModulationReviewGroup
2017
Tuning Neuronal Potassium Channels to the Auditory Environment
Kaczmarek L. Tuning Neuronal Potassium Channels to the Auditory Environment. Springer Handbook Of Auditory Research 2017, 64: 133-159. DOI: 10.1007/978-3-319-21530-3_6.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsBrainstem nucleiPotassium channelsAuditory brainstem nucleiVoltage-dependent potassium channelsNeuronal potassium channelsAuditory discrimination taskAuditory neuronsAuditory environmentChannel isoformsNeuronsHigh rateAuditory informationKv3.1Molecular mechanismsDifferent auditory environmentsRapid alterationsDiscrimination taskKv3 Channels: Enablers of Rapid Firing, Neurotransmitter Release, and Neuronal Endurance
Kaczmarek LK, Zhang Y. Kv3 Channels: Enablers of Rapid Firing, Neurotransmitter Release, and Neuronal Endurance. Physiological Reviews 2017, 97: 1431-1468. PMID: 28904001, PMCID: PMC6151494, DOI: 10.1152/physrev.00002.2017.Peer-Reviewed Original ResearchConceptsKv3 channelsAuditory brain stem neuronsNeurotransmitter releaseBrain stem neuronsOngoing neuronal activityFire action potentialsHigh-frequency firingChannel genesStem neuronsGABAergic interneuronsMultiple protein isoformsCertain neuronsProtein-protein interactionsNeuronal activityNeuronal functionAlzheimer's diseaseNeurological disordersAction potentialsPurkinje cellsUnique expression patternKv3 familyNeuronsAbnormal regulationProtein isoformsProtein kinase
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
2015
Signaling in the Brain
Levitan I, Kaczmarek L. Signaling in the Brain. 2015, 3-22. DOI: 10.1093/med/9780199773893.003.0001.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsElectrical Signaling in Neurons
Levitan I, Kaczmarek L. Electrical Signaling in Neurons. 2015, 41-62. DOI: 10.1093/med/9780199773893.003.0003.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsNeurotransmitters and Neurohormones
Levitan I, Kaczmarek L. Neurotransmitters and Neurohormones. 2015, 213-238. DOI: 10.1093/med/9780199773893.003.0010.ChaptersNervous systemNearby glial cellsRole of neurotransmittersSpecific transporter proteinsExtracellular spaceGlial cellsNerve terminalsPresynaptic terminalsTransporter proteinsIntercellular communicationTarget cellsGreat diversityNeuropeptidesNeurotransmittersMultitude of chemicalsCellsAcetylcholineReuptakeCatecholaminesGABANeuronsNeurohormonesThe Birth and Death of a Neuron
Levitan I, Kaczmarek L. The Birth and Death of a Neuron. 2015, 329-352. DOI: 10.1093/med/9780199773893.003.0014.ChaptersNervous systemComplement of genesOuter mitochondrial membraneBone morphogenetic proteinNew neuronsNeuronal determinationTranscription factorsMitochondrial membraneBrain regionsMorphogenetic proteinsNeural inducersSpecific neuronsNeuronsEarly stepsNormal formationAction of factorsHigh rateDeathBirthVariety of factorsCellsFactorsGenesForm and Function in Cells of the Brain
Levitan I, Kaczmarek L. Form and Function in Cells of the Brain. 2015, 23-38. DOI: 10.1093/med/9780199773893.003.0002.ChaptersNeuronal Growth and Trophic Factors
Levitan I, Kaczmarek L. Neuronal Growth and Trophic Factors. 2015, 353-386. DOI: 10.1093/med/9780199773893.003.0015.ChaptersMolecular genetic approachesMature nervous systemGrowth factorNeuronal determinationTranscription factorsGenetic approachesKey growth factorsNeural developmentStem cellsTypes of neuronsNearby cellsNeuronal growthMechanism of actionMedical therapySympathetic neuronsMotor neuronsTrophic factorsNervous systemSteroid hormonesNeuronsDrosophilaCellsDevelopmental factorsGeneticsDifferentiationIntrinsic Neuronal Properties, Neural Networks, and Behavior
Levitan I, Kaczmarek L. Intrinsic Neuronal Properties, Neural Networks, and Behavior. 2015, 457-488. DOI: 10.1093/med/9780199773893.003.0018.ChaptersAction of neurotransmittersIntrinsic neuronal propertiesIntrinsic excitabilityStomatogastric ganglionCommand neuronsNeuronal propertiesDendritic treeAction potentialsNeuronsCellular mechanismsNetwork activitySensory informationIntrinsic electrical propertiesGangliaExcitabilityMost behaviorsNeurotransmittersHormone
2014
Emerging role of the KCNT1 Slack channel in intellectual disability
Kim GE, Kaczmarek LK. Emerging role of the KCNT1 Slack channel in intellectual disability. Frontiers In Cellular Neuroscience 2014, 8: 209. PMID: 25120433, PMCID: PMC4112808, DOI: 10.3389/fncel.2014.00209.Peer-Reviewed Original ResearchIntellectual disabilitySlack channelsChannel activityEarly-onset epilepsyMaintained stimulationOnset epilepsyFragile X syndromeCommon causeNeuronal excitabilityEpileptic disordersAnimal modelsIntellectual impairmentX syndromeDisabilityMental retardation proteinSyndromePhysiological roleEpilepsyKCNT1ExcitabilityNeuronsBrainImpairmentRoleActivity
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