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
Interaction Between HCN and Slack Channels Regulates mPFC Pyramidal Cell Excitability in Working Memory Circuits
Wu J, El-Hassar L, Datta D, Thomas M, Zhang Y, Jenkins D, DeLuca N, Chatterjee M, Gribkoff V, Arnsten A, Kaczmarek L. Interaction Between HCN and Slack Channels Regulates mPFC Pyramidal Cell Excitability in Working Memory Circuits. Molecular Neurobiology 2023, 61: 2430-2445. PMID: 37889366, DOI: 10.1007/s12035-023-03719-8.Peer-Reviewed Original ResearchPFC pyramidal neuronsPyramidal cellsHCN channelsPrefrontal cortexPyramidal neuronsNeuronal firingSlack channelsPyramidal cell excitabilityRat prefrontal cortexPFC pyramidal cellsCell linesNon-selective cation channelsRecurrent excitatory connectionsCortical extractsNeuronal depolarizationNeuronal excitabilityPharmacological blockersSpecific blockerDendritic spinesKNa channelsCell excitabilityPostsynaptic spinesPersistent firingExcitatory connectionsNeural circuits
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
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
Receptors and Transduction Mechanisms II: Indirectly Coupled Receptor/Ion Channel Systems
Levitan I, Kaczmarek L. Receptors and Transduction Mechanisms II: Indirectly Coupled Receptor/Ion Channel Systems. 2015, 263-294. DOI: 10.1093/med/9780199773893.003.0012.ChaptersProtein phosphorylationSecond messenger-dependent protein kinasesReceptor-channel couplingIon channel proteinsAppropriate biological responseExtracellular signalsDirect phosphorylationSpecific membrane receptorsProtein kinaseRegulatory componentsChannel proteinsSecond messenger systemsMembrane receptorsTransduction mechanismsIon channelsPhosphorylationBiological responsesMessenger systemsIon channel systemsDiversityTarget cellsSignal recognitionNeuronal excitabilityCellsKinase
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
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
Regulation of Neuronal Excitability by the Sodium‐Activated Potassium Channels Slick (SLO2.1) and Slack (SLO2.2)
Gribkoff V, Kaczmarek L. Regulation of Neuronal Excitability by the Sodium‐Activated Potassium Channels Slick (SLO2.1) and Slack (SLO2.2). 2008, 193-215. DOI: 10.1002/9780470429907.ch7.ChaptersRepetitive 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
Opposite Regulation of Slick and Slack K+ Channels by Neuromodulators
Santi CM, Ferreira G, Yang B, Gazula VR, Butler A, Wei A, Kaczmarek LK, Salkoff L. Opposite Regulation of Slick and Slack K+ Channels by Neuromodulators. Journal Of Neuroscience 2006, 26: 5059-5068. PMID: 16687497, PMCID: PMC6674240, DOI: 10.1523/jneurosci.3372-05.2006.Peer-Reviewed Original ResearchConceptsSlo2 channelsHippocampal brain sectionsCultured hippocampal neuronsProtein kinase CWhole-cell currentsPKC activator PMANeuronal excitabilityHippocampal neuronsBrain sectionsBasal levelsImmunocytochemical techniquesGalphaq proteinElectrical activitySlo2.1Activator PMAReceptorsChannel gene familyWidespread expressionChannel activityExcitabilityNeuromodulatorsIntracellular concentrationPotential of cellsBrainXenopus oocytesPolicing 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
For K+ channels, Na+ is the new Ca2+
Bhattacharjee A, Kaczmarek LK. For K+ channels, Na+ is the new Ca2+. Trends In Neurosciences 2005, 28: 422-428. PMID: 15979166, DOI: 10.1016/j.tins.2005.06.003.Peer-Reviewed Original Research
2003
BAK 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 roleExcitability
2001
Receptors and Transduction Mechanisms II: Indirectly Coupled Receptor/Ion Channel Systems
B.Levitan I, Kaczmarek L. Receptors and Transduction Mechanisms II: Indirectly Coupled Receptor/Ion Channel Systems. 2001, 285-314. DOI: 10.1093/oso/9780195145236.003.0012.Peer-Reviewed Original ResearchExtracellular signalsSingle protein complexIon channel familyMembrane ion channelsBiological responsesFamily of receptorsProtein complexesIntercellular communicationTarget cellsChannel familyIon channelsIon channel systemsCellsSpecific receptorsNeuronal excitabilityParticular target cellsFinal stepReceptorsFamilyTransductionBiochemistryComplexesResponseExcitabilityNeurons
1998
Heterologous Expression of the Kv3.1 Potassium Channel Eliminates Spike Broadening and the Induction of a Depolarizing Afterpotential in the Peptidergic Bag Cell Neurons
Whim M, Kaczmarek L. Heterologous Expression of the Kv3.1 Potassium Channel Eliminates Spike Broadening and the Induction of a Depolarizing Afterpotential in the Peptidergic Bag Cell Neurons. Journal Of Neuroscience 1998, 18: 9171-9180. PMID: 9801357, PMCID: PMC6792887, DOI: 10.1523/jneurosci.18-22-09171.1998.Peer-Reviewed Original ResearchConceptsBag cell neuronsCell neuronsAction potentialsCalcium entryUse-dependent inactivationExpression of Kv3.1Kv3.1 potassium channelPeptidergic bag cell neuronsControl neuronsSpontaneous firingBrief synaptic stimulationCalcium currentNeuronal excitabilityIntracellular calciumCalcium influxSynaptic stimulationDepolarizing afterpotentialsBAPTA-AMAfterpotentialsNeuronsPotassium channelsClusters of cellsKv3.1InductionPhysiological roleDepolarization 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 increase
1996
Identification and Characterization of a Ca2+-Sensitive Nonspecific Cation Channel Underlying Prolonged Repetitive Firing in Aplysia Neurons
Wilson G, Richardson F, Fisher T, Olivera B, Kaczmarek L. Identification and Characterization of a Ca2+-Sensitive Nonspecific Cation Channel Underlying Prolonged Repetitive Firing in Aplysia Neurons. Journal Of Neuroscience 1996, 16: 3661-3671. PMID: 8642410, PMCID: PMC6578840, DOI: 10.1523/jneurosci.16-11-03661.1996.Peer-Reviewed Original ResearchConceptsNonspecific cation channelRepetitive firingCation channelsSpontaneous repetitive firingNeuronal response propertiesBag cell neuronsSlow inwardNeuronal excitabilityCell neuronsChannels underliesProlonged dischargeAplysia bag cell neuronsAplysia neuronsAfterdischargesNeuronsPhosphorylation-mediated changesResponse propertiesChannel recordingsConus textileFiringO mVTetrodotoxinExcitabilityRegulation of potassium channels by protein kinases
Jonas E, Kaczmarek L. Regulation of potassium channels by protein kinases. Current Opinion In Neurobiology 1996, 6: 318-323. PMID: 8794088, DOI: 10.1016/s0959-4388(96)80114-0.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
1993
Mode-switching of a voltage-gated cation channel is mediated by a protein kinase A-regulated tyrosine phosphatase
Wilson G, Kaczmarek L. Mode-switching of a voltage-gated cation channel is mediated by a protein kinase A-regulated tyrosine phosphatase. Nature 1993, 366: 433-438. PMID: 8247151, DOI: 10.1038/366433a0.Peer-Reviewed Original ResearchConceptsVoltage-gated cation channelsTyrosine phosphataseProtein kinase A. MoreoverProtein kinase ACation channelsAplysia bag cell neuronsBag cell neuronsKinase ATyrosine kinasePatch-clamp studiesPhosphataseGating modesCell neuronsA. MoreoverNeuronal excitabilityNervous system tissueKinaseCentral nervous system tissueEnzyme
1989
Protein kinase inhibitors selectively block phorbol ester- or forskolin- induced changes in excitability of Aplysia neurons
Conn P, Strong J, Azhderian E, Nairn A, Greengard P, Kaczmarek L. Protein kinase inhibitors selectively block phorbol ester- or forskolin- induced changes in excitability of Aplysia neurons. Journal Of Neuroscience 1989, 9: 473-479. PMID: 2537389, PMCID: PMC6569795, DOI: 10.1523/jneurosci.09-02-00473.1989.Peer-Reviewed Original ResearchConceptsProtein kinase CBag cell neuronsVoltage-dependent calcium currentsCAMP-PKPhorbol esterKinase CCell neuronsAction potentialsCalcium currentInhibitor of PKCProtein kinase inhibitorsPhorbol ester-induced enhancementKinase inhibitor 1Protein kinase inhibitor 1Adenylate cyclase activator forskolinCyclase activator forskolinProtein inhibitorGranule movementVoltage-dependent currentsCell action potentialsCAMP analogEffect of forskolinActivator forskolinPhorbol ester-induced changesNeuronal excitability