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 ResearchMeSH KeywordsAction PotentialsAuditory PathwaysMembrane PotentialsPhosphorylationPotassiumPotassium ChannelsConceptsPotassium 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
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
International Union of Basic and Clinical Pharmacology. C. Nomenclature and Properties of Calcium-Activated and Sodium-Activated Potassium Channels
Kaczmarek LK, Aldrich RW, Chandy KG, Grissmer S, Wei AD, Wulff H. International Union of Basic and Clinical Pharmacology. C. Nomenclature and Properties of Calcium-Activated and Sodium-Activated Potassium Channels. Pharmacological Reviews 2016, 69: 1-11. PMID: 28267675, PMCID: PMC11060434, DOI: 10.1124/pr.116.012864.Peer-Reviewed Original ResearchStimulation 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
Human Slack Potassium Channel Mutations Increase Positive Cooperativity between Individual Channels
Kim GE, Kronengold J, Barcia G, Quraishi IH, Martin HC, Blair E, Taylor JC, Dulac O, Colleaux L, Nabbout R, Kaczmarek LK. Human Slack Potassium Channel Mutations Increase Positive Cooperativity between Individual Channels. Cell Reports 2014, 9: 1661-1672. PMID: 25482562, PMCID: PMC4294418, DOI: 10.1016/j.celrep.2014.11.015.Peer-Reviewed Original ResearchUse of label-free optical biosensors to detect modulation of potassium channels by G-protein coupled receptors.
Fleming MR, Shamah SM, Kaczmarek LK. Use of label-free optical biosensors to detect modulation of potassium channels by G-protein coupled receptors. Journal Of Visualized Experiments 2014, e51307. PMID: 24562095, PMCID: PMC4122194, DOI: 10.3791/51307.Peer-Reviewed Original ResearchConceptsG protein-coupled receptorsOptical biosensorPlasma membraneLabel-free optical biosensorProtein-protein interactionsIon channelsChannel-protein interactionsExcitable cell typesReceptor tyrosine kinasesProtein-coupled receptorsLigand-induced changesCell surface receptorsPotassium channelsRegulatory proteinsTyrosine kinaseG proteinsProtein behaviorSodium-activated potassium channelsExogenous labelsPhysiological relevanceCell adhesionLiving cellsCell typesHeteromeric channelsSurface receptorsClinical whole-genome sequencing in severe early-onset epilepsy reveals new genes and improves molecular diagnosis
Martin HC, Kim GE, Pagnamenta AT, Murakami Y, Carvill GL, Meyer E, Copley RR, Rimmer A, Barcia G, Fleming MR, Kronengold J, Brown MR, Hudspith KA, Broxholme J, Kanapin A, Cazier JB, Kinoshita T, Nabbout R, Consortium T, Bentley D, McVean G, Heavin S, Zaiwalla Z, McShane T, Mefford HC, Shears D, Stewart H, Kurian MA, Scheffer IE, Blair E, Donnelly P, Kaczmarek LK, Taylor JC. Clinical whole-genome sequencing in severe early-onset epilepsy reveals new genes and improves molecular diagnosis. Human Molecular Genetics 2014, 23: 3200-3211. PMID: 24463883, PMCID: PMC4030775, DOI: 10.1093/hmg/ddu030.Peer-Reviewed Original ResearchMeSH KeywordsChildChild, PreschoolChromosomes, Human, Pair 9EpilepsyGenetic Predisposition to DiseaseGenome-Wide Association StudyHigh-Throughput Nucleotide SequencingHumansKCNQ2 Potassium ChannelMaleMembrane ProteinsMutationNAV1.2 Voltage-Gated Sodium ChannelNerve Tissue ProteinsPathology, MolecularPotassium ChannelsPotassium Channels, Sodium-ActivatedProto-Oncogene Proteins c-cblUniparental DisomyYoung AdultConceptsSevere early-onset epilepsyEarly-onset epilepsyOhtahara syndromeMolecular diagnosisWhole-genome sequencingClinical whole-genome sequencingPathogenic de novo mutationsHomozygous missense variantPotassium channel currentsSeizure typesO patientsDiagnostic yieldOS casesPatientsPower of WGSMolecular genetic diagnosisEpilepsyClinical phenotypeClinical diagnosisClinical toolHeterogeneous disorderDevelopmental delayDe novo mutationsDiagnosisMissense variants
2013
A sodium-activated potassium channel supports high-frequency firing and reduces energetic costs during rapid modulations of action potential amplitude
Markham MR, Kaczmarek LK, Zakon HH. A sodium-activated potassium channel supports high-frequency firing and reduces energetic costs during rapid modulations of action potential amplitude. Journal Of Neurophysiology 2013, 109: 1713-1723. PMID: 23324315, PMCID: PMC3628015, DOI: 10.1152/jn.00875.2012.Peer-Reviewed Original Research
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
2011
Potassium channel modulation and auditory processing
Brown MR, Kaczmarek LK. Potassium channel modulation and auditory processing. Hearing Research 2011, 279: 32-42. PMID: 21414395, PMCID: PMC3137660, DOI: 10.1016/j.heares.2011.03.004.Peer-Reviewed Original ResearchConceptsAuditory brainstem nucleiBrainstem nucleiPotassium channelsPotassium channel modulationSynaptic stimulationFiring patternsOverall sensitivityChannel modulationNeuronsAuditory environmentAuditory processingAuditory systemHigh rateAuditory informationIntrinsic electrical propertiesKey proteinsReview article
2010
Fragile X mental retardation protein controls gating of the sodium-activated potassium channel Slack
Brown MR, Kronengold J, Gazula VR, Chen Y, Strumbos JG, Sigworth FJ, Navaratnam D, Kaczmarek LK. Fragile X mental retardation protein controls gating of the sodium-activated potassium channel Slack. Nature Neuroscience 2010, 13: 819-821. PMID: 20512134, PMCID: PMC2893252, DOI: 10.1038/nn.2563.Peer-Reviewed Original ResearchControlling auditory excitability: the benefits of a cultured environment
Kaczmarek LK. Controlling auditory excitability: the benefits of a cultured environment. The Journal Of Physiology 2010, 588: 1387-1388. PMID: 20436041, PMCID: PMC2876793, DOI: 10.1113/jphysiol.2010.189712.Peer-Reviewed Original ResearchThe 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
2009
Use of optical biosensors to detect modulation of Slack potassium channels by G protein-coupled receptors
Fleming MR, Kaczmarek LK. Use of optical biosensors to detect modulation of Slack potassium channels by G protein-coupled receptors. Journal Of Receptors And Signal Transduction 2009, 29: 173-181. PMID: 19640220, PMCID: PMC3727623, DOI: 10.1080/10799890903056883.Peer-Reviewed Original ResearchConceptsG protein-coupled receptorsProtein-coupled receptorsPlasma membraneIon channelsActivation of GPCRsProtein-protein interactionsDistribution of massExcitable cell typesPotassium channelsRefractive indexHeteromeric channel complexesOptical sensorsOptical biosensorSlack potassium channelsSurface of cellsRegulatory proteinsMass distributionGPCR activationSodium-activated potassium channelsLiving cellsCell typesElectrical propertiesChannel complexBiophysical propertiesProteinThe N-Terminal Domain of Slack Determines the Formation and Trafficking of Slick/Slack Heteromeric Sodium-Activated Potassium Channels
Chen H, Kronengold J, Yan Y, Gazula VR, Brown MR, Ma L, Ferreira G, Yang Y, Bhattacharjee A, Sigworth FJ, Salkoff L, Kaczmarek LK. The N-Terminal Domain of Slack Determines the Formation and Trafficking of Slick/Slack Heteromeric Sodium-Activated Potassium Channels. Journal Of Neuroscience 2009, 29: 5654-5665. PMID: 19403831, PMCID: PMC3688047, DOI: 10.1523/jneurosci.5978-08.2009.Peer-Reviewed Original ResearchConceptsTerminal domainN-terminal domainAlternative splice variantsPotassium channelsSubcellular localizationPlasma membraneMolecular explanationHeteromer formationSplice variantsHeteromeric channelsDistinct rolesSingle-channel levelSubunitsUnitary conductanceCentral neuronsSlack channelsImmunocytochemical studyFiring patternsDomainLocalizationNeuronsGenesTraffickingChannel levelHomomers
2008
Amino‐termini isoforms of the Slack K+ channel, regulated by alternative promoters, differentially modulate rhythmic firing and adaptation
Brown MR, Kronengold J, Gazula V, Spilianakis CG, Flavell RA, Von Hehn CA, Bhattacharjee A, Kaczmarek LK. Amino‐termini isoforms of the Slack K+ channel, regulated by alternative promoters, differentially modulate rhythmic firing and adaptation. The Journal Of Physiology 2008, 586: 5161-5179. PMID: 18787033, PMCID: PMC2652154, DOI: 10.1113/jphysiol.2008.160861.Peer-Reviewed Original ResearchAction PotentialsAdaptation, PhysiologicalAmino Acid SequenceAnimalsBrainCloning, MolecularGene Expression RegulationMiceMice, Inbred C57BLMolecular Sequence DataNerve Tissue ProteinsNeuronsPotassium ChannelsPotassium Channels, Sodium-ActivatedPromoter Regions, GeneticProtein IsoformsRatsRNA, Messenger
2007
Sodium‐dependent potassium channels of a Slack‐like subtype contribute to the slow afterhyperpolarization in lamprey spinal neurons
Wallén P, Robertson B, Cangiano L, Löw P, Bhattacharjee A, Kaczmarek LK, Grillner S. Sodium‐dependent potassium channels of a Slack‐like subtype contribute to the slow afterhyperpolarization in lamprey spinal neurons. The Journal Of Physiology 2007, 585: 75-90. PMID: 17884929, PMCID: PMC2375474, DOI: 10.1113/jphysiol.2007.138156.Peer-Reviewed Original ResearchConceptsSodium-dependent potassium channelSlow afterhyperpolarizationAction potentialsPotassium channelsSingle action potentialLamprey spinal neuronsLamprey spinal cordLamprey locomotor networkSlow AHPLarge neuronsSpinal neuronsSpinal cordLocomotor networksBurst activityKNa channelsDistinct immunoreactivityGray matterReversal potentialNeuronsChloride injectionAfterhyperpolarizationRapid activationFunctional roleHigh-level activitiesSlack geneSlack and Slick KNa Channels Regulate the Accuracy of Timing of Auditory Neurons
Yang B, Desai R, Kaczmarek LK. Slack and Slick KNa Channels Regulate the Accuracy of Timing of Auditory Neurons. Journal Of Neuroscience 2007, 27: 2617-2627. PMID: 17344399, PMCID: PMC6672517, DOI: 10.1523/jneurosci.5308-06.2007.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAnimals, NewbornAuditory PathwaysBithionolBrain StemComputer SimulationElectric ConductivityElectric StimulationElectrophysiologyIn Vitro TechniquesMiceModels, NeurologicalNerve Tissue ProteinsNeuronsNeurons, AfferentPotassium ChannelsPotassium Channels, Sodium-ActivatedReaction TimeSodium