2022
The role of altered translation in intellectual disability and epilepsy
Malone TJ, Kaczmarek LK. The role of altered translation in intellectual disability and epilepsy. Progress In Neurobiology 2022, 213: 102267. PMID: 35364140, PMCID: PMC10583652, DOI: 10.1016/j.pneurobio.2022.102267.Peer-Reviewed Original ResearchConceptsIntellectual disabilityNeuronal stimulationLocal synaptic activityActivity-dependent changesActivity-dependent translationOverall excitabilitySynaptic activityEpileptic seizuresSynaptic componentsCellular compositionEpilepsyDisabilityIon channelsCell typesDisordersHigher proportionStimulationSeizuresStimuliWorld populationPopulationExcitabilityOriginal stimulusDiseaseMutations
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 Research
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
2015
Intrinsic 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
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
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 stepReceptorsFamilyTransductionBiochemistryComplexesResponseExcitabilityNeuronsTargeted 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 TransmissionTransgenes
1998
Expression of a foreign G-protein coupled receptor modulates the excitability of the peptidergic bag cell neurons of Aplysia
Whim M, Kaczmarek L. Expression of a foreign G-protein coupled receptor modulates the excitability of the peptidergic bag cell neurons of Aplysia. Neuroscience Letters 1998, 258: 143-146. PMID: 9885951, DOI: 10.1016/s0304-3940(98)00850-7.Peer-Reviewed Original ResearchConceptsBag cell neuronsCell neuronsMetabotropic glutamate receptorsG proteinsPeptidergic bag cell neuronsAfferent stimulationSpontaneous firingAfferent inputGlutamate receptorsSecond messenger pathwaysPharmacological activationReceptor activationAfterdischargesNeuronsMessenger pathwaysReceptorsActivationAdditional pathwaysExpressionExcitabilityPathwaySustained periodFormation of intermediate-conductance calcium-activated potassium channels by interaction of Slack and Slo subunits
Joiner W, Tang M, Wang L, Dworetzky S, Boissard C, Gan L, Gribkoff V, Kaczmarek L. Formation of intermediate-conductance calcium-activated potassium channels by interaction of Slack and Slo subunits. Nature Neuroscience 1998, 1: 462-469. PMID: 10196543, DOI: 10.1038/2176.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsElectric ConductivityIntermediate-Conductance Calcium-Activated Potassium ChannelsIsomerismLarge-Conductance Calcium-Activated Potassium ChannelsMolecular Sequence DataNerve Tissue ProteinsPotassium ChannelsPotassium Channels, Calcium-ActivatedPotassium Channels, Sodium-ActivatedConceptsCalcium-activated potassium channelsIntracellular calciumNervous systemIntermediate-conductance calcium-activated potassium channelsPotassium channelsLarge-conductance calcium-activated potassium channelsControl of excitabilitySlo subunitIntermediate conductance channelPotassium channel genesPharmacological propertiesIntermediate conductanceCytoplasmic calciumChannel subunitsSlo channelsSlack channelsChannel genesSingle-channel conductanceUnitary conductanceCalciumExcitabilitySLOSecretion
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 mVTetrodotoxinExcitability
1988
Steroidal Regulation of mRNA Coding for Potassium Channels in Uterine Smooth Muscle
Boyle M, Kaczmarek L. Steroidal Regulation of mRNA Coding for Potassium Channels in Uterine Smooth Muscle. 1988, 359-368. DOI: 10.1007/978-1-4613-0975-8_29.Peer-Reviewed Original ResearchSmooth muscleAdministration of steroidsCourse of pregnancySmooth muscle excitabilityEnd of pregnancyUterine smooth muscleEstrogen treatmentElectrophysiological changesOvariectomized animalsProgesterone levelsHormonal statusEstrogen concentrationsMuscle excitabilitySteroidal regulationMammalian uterusSteroid hormonesPregnancyPotassium channelsProlonged changesUterusExcitabilityExcitable tissuesMuscleAnimalsQuiescent state
1987
Hormonal regulation of K+-channel messenger RNA in rat myometrium during oestrus cycle and in pregnancy
Boyle M, MacLusky N, Naftolin F, Kaczmarek L. Hormonal regulation of K+-channel messenger RNA in rat myometrium during oestrus cycle and in pregnancy. Nature 1987, 330: 373-375. PMID: 2446134, DOI: 10.1038/330373a0.Peer-Reviewed Original ResearchConceptsChannel messenger RNAUterine smooth muscle cellsSmooth muscle excitabilityEnd of pregnancyPresence of estrogenSmooth muscle cellsIon channelsEstrogen altersPregnant ratsHormonal treatmentMyometrial cellsRat myometriumSteroid hormonesMuscle cellsOestrous cycleCellular excitabilityOestrus cycleVoltage-dependent ion channelsHormonal regulationPregnancyEstrogenExcitabilityElectrical couplingMessenger RNAMessenger RNA species