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
2019
Phactr1 regulates Slack (KCNT1) channels via protein phosphatase 1 (PP1)
Ali SR, Malone TJ, Zhang Y, Prechova M, Kaczmarek LK. Phactr1 regulates Slack (KCNT1) channels via protein phosphatase 1 (PP1). The FASEB Journal 2019, 34: 1591-1601. PMID: 31914597, PMCID: PMC6956700, DOI: 10.1096/fj.201902366r.Peer-Reviewed Original ResearchConceptsProtein phosphatase 1Phosphatase 1Binding of PP1C-terminusCytoplasmic signaling proteinsCytoplasmic C-terminusActin-binding proteinsSlack channelsPKC phosphorylation sitesPhosphoprotein substratesDisease-causing mutationsPhosphorylation sitesSignaling proteinsSlack currentsHuman mutationsSodium-activated potassium channelsPHACTR1Slack genePotassium channelsProteinActinMutationsPatch-clamp recordingsCentral nervous systemMutants
2018
C-terminal proline deletions in KCNC3 cause delayed channel inactivation and an adult-onset progressive SCA13 with spasticity
Khare S, Galeano K, Zhang Y, Nick JA, Nick HS, Subramony SH, Sampson J, Kaczmarek LK, Waters MF. C-terminal proline deletions in KCNC3 cause delayed channel inactivation and an adult-onset progressive SCA13 with spasticity. The Cerebellum 2018, 17: 692-697. PMID: 29949095, PMCID: PMC8299775, DOI: 10.1007/s12311-018-0950-5.Peer-Reviewed Original ResearchConceptsIon channel functionMammalian cell cultureMutant proteinsIntracellular cSpinocerebellar ataxia 13Autosomal dominant neurological diseaseChannel functionAllelic heterogeneityProline deletionSCA13 patientsTerminal portionProgressive clinical symptomsNormal membranesCell culturesProteinElectrophysiological characterizationChannel inactivationInactivationClinical symptomsElectrophysiological profileNeurological diseasesClinical importanceSCA13Slow inactivationDeletion
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
2014
Disrupted in Schizophrenia 1 Modulates Medial Prefrontal Cortex Pyramidal Neuron Activity Through cAMP Regulation of Transient Receptor Potential C and Small-Conductance K+ Channels
El-Hassar L, Simen AA, Duque A, Patel KD, Kaczmarek LK, Arnsten AF, Yeckel MF. Disrupted in Schizophrenia 1 Modulates Medial Prefrontal Cortex Pyramidal Neuron Activity Through cAMP Regulation of Transient Receptor Potential C and Small-Conductance K+ Channels. Biological Psychiatry 2014, 76: 476-485. PMID: 24560582, PMCID: PMC4104266, DOI: 10.1016/j.biopsych.2013.12.019.Peer-Reviewed Original ResearchConceptsCyclic adenosine monophosphateIntracellular Ca2Prefrontal cortical pyramidal neuronsReceptor-mediated intracellular Ca2Regulation of cAMPPrefrontal cortical slicesCortical pyramidal neuronsDISC1 functionMajor depressive disorderPyramidal neuron activityPatch-clamp recordingsTRPC channel activityDISC1 disruptionPrefrontal cortex activityPyramidal neuronsCortical slicesDepressive disorderAdult ratsIntracellular calcium wavesSustained depolarizationViral knockdownNeuron activityBipolar disorderMental disordersCAMP generation
2012
An evolutionarily conserved mode of modulation of Shaw‐like K+ channels
Cotella D, Hernandez‐Enriquez B, Duan Z, Wu X, Gazula V, Brown MR, Kaczmarek LK, Sesti F. An evolutionarily conserved mode of modulation of Shaw‐like K+ channels. The FASEB Journal 2012, 27: 1381-1393. PMID: 23233530, PMCID: PMC3606535, DOI: 10.1096/fj.12-222778.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain StemCaenorhabditis elegansEvolution, MolecularMembrane PotentialsMiceMice, Inbred C57BLNeuronsPhosphorylationShaw Potassium ChannelsConceptsEffect of phosphorylationC. elegansACP-2Acid phosphataseMammalian homologMammalian homologueCaenorhabditis elegansMouse nervous systemRegulatory partnersBiochemical experimentsMolecular mechanismsElegansBehavioral defectsMode of modulationPhosphorylationPharmacological disruptionShaw familyMammalian brainSubset of neuronsVentricular zonePhosphataseModel systemNervous systemMice resultsElectrophysiological analysis
2010
Kv1.3 is the exclusive voltage‐gated K+ channel of platelets and megakaryocytes: roles in membrane potential, Ca2+ signalling and platelet count
McCloskey C, Jones S, Amisten S, Snowden RT, Kaczmarek LK, Erlinge D, Goodall AH, Forsythe ID, Mahaut‐Smith M. Kv1.3 is the exclusive voltage‐gated K+ channel of platelets and megakaryocytes: roles in membrane potential, Ca2+ signalling and platelet count. The Journal Of Physiology 2010, 588: 1399-1406. PMID: 20308249, PMCID: PMC2876798, DOI: 10.1113/jphysiol.2010.188136.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood PlateletsCalcium SignalingCell SizeDNA, ComplementaryHumansIn Vitro TechniquesKv1.3 Potassium ChannelMegakaryocytesMembrane PotentialsMiceMice, Inbred C57BLPatch-Clamp TechniquesPlatelet CountReverse Transcriptase Polymerase Chain ReactionScorpion VenomsSecond Messenger SystemsConceptsLarge ionic conductanceMembrane potentialHuman plateletsKv alphaMegakaryocyte developmentAncillary subunitsQuantitative RT-PCRMolecular levelKv channelsRole of Kv1.3MegakaryocytesKv1.3RT-PCRWild-type miceKv currentsSubunitsSignalingMiceApoptosisMargatoxinPlatelet activationRoleIonic conductancesPlateletsActivationThe 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
2008
Na+-mediated coupling between AMPA receptors and KNa channels shapes synaptic transmission
Nanou E, Kyriakatos A, Bhattacharjee A, Kaczmarek LK, Paratcha G, Manira A. Na+-mediated coupling between AMPA receptors and KNa channels shapes synaptic transmission. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 20941-20946. PMID: 19095801, PMCID: PMC2634910, DOI: 10.1073/pnas.0806403106.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsLampreysMembrane PotentialsNeuronsRatsReceptors, AMPASodium-Potassium-Chloride SymportersSynapsesSynaptic TransmissionRepetitive 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
2007
Bcl-xL Inhibitor ABT-737 Reveals a Dual Role for Bcl-xL in Synaptic Transmission
Hickman JA, Hardwick JM, Kaczmarek LK, Jonas EA. Bcl-xL Inhibitor ABT-737 Reveals a Dual Role for Bcl-xL in Synaptic Transmission. Journal Of Neurophysiology 2007, 99: 1515-1522. PMID: 18160428, PMCID: PMC2836590, DOI: 10.1152/jn.00598.2007.Peer-Reviewed Original ResearchConceptsMitochondrial outer membraneEndogenous Bcl-xLMitochondrial channel activityBcl-xLInhibitor ABT-737ABT-737Outer membraneBcl-xL.Pro-apoptotic cleavage productRecombinant Bcl-xLChannel activityBcl-xL proteinSynaptic functionDual roleGenetic toolsDomain pocketSynaptic transmissionSynaptic activityGiant presynaptic terminalEquivalent modificationEndogenous proteolysisRepetitive synaptic activityBH3Cleavage productsProtein
2006
A Store-Operated Ca2+ Influx Pathway in the Bag Cell Neurons of Aplysia
Kachoei BA, Knox RJ, Uthuza D, Levy S, Kaczmarek LK, Magoski NS. A Store-Operated Ca2+ Influx Pathway in the Bag Cell Neurons of Aplysia. Journal Of Neurophysiology 2006, 96: 2688-2698. PMID: 16885525, PMCID: PMC2894935, DOI: 10.1152/jn.00118.2006.Peer-Reviewed Original ResearchMeSH KeywordsAnilidesAnimalsAplysiaCalcium Channel BlockersCalcium ChannelsCalcium SignalingElectrophysiologyEnzyme InhibitorsImidazolesIn Vitro TechniquesIndicators and ReagentsIndolesInositol 1,4,5-TrisphosphateLanthanumMacrocyclic CompoundsMembrane PotentialsNeuronsNickelOxazolesRyanodine Receptor Calcium Release ChannelThapsigarginThiadiazolesConceptsBag cell neuronsCell neuronsCyclopiazonic acidCPA-sensitive storesSmooth muscle cell lineAbsence of extracellularCultured bag cell neuronsRyanodine receptor agonistATPase inhibitorReceptor blockersReceptor agonistNeuropeptide secretionXestospongin CMuscle cell lineInflux pathwayIntracellular storesNonneuronal cellsAcidic storesElevated intracellularNeuronsStore depletionAfterdischargesCell linesBafilomycin AEntry pathwayPharmacological activation and inhibition of Slack (Slo2.2) channels
Yang B, Gribkoff VK, Pan J, Damagnez V, Dworetzky SI, Boissard CG, Bhattacharjee A, Yan Y, Sigworth FJ, Kaczmarek LK. Pharmacological activation and inhibition of Slack (Slo2.2) channels. Neuropharmacology 2006, 51: 896-906. PMID: 16876206, DOI: 10.1016/j.neuropharm.2006.06.003.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Infective Agents, LocalBepridilBithionolCalcium Channel BlockersCell Line, TransformedDose-Response Relationship, DrugDose-Response Relationship, RadiationElectric StimulationEnzyme ActivationEnzyme InhibitorsHumansMembrane PotentialsOocytesPatch-Clamp TechniquesPotassium Channels, Calcium-ActivatedQuinidineTransfectionXenopusConceptsSlack channelsConcentration-dependent mannerIschemic injuryPharmacological activationKNa channelsMammalian brainFiring ratePharmacological propertiesChannel subunitsReversible increaseChannel activityCell linesBepridilHEK cellsRobust activatorNeuronsStable cell linesInhibitionExcised patchesXenopus oocytesPresent studyBithionolChannel openingSpecific roleMembrane patchesOpposite 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 ResearchMeSH KeywordsAnimalsHumansKv1.2 Potassium ChannelMembrane PotentialsModels, BiologicalNeural InhibitionProtein Subunits
2005
Requirement of Voltage-Gated Calcium Channel ß4 Subunit for T Lymphocyte Functions
Badou A, Basavappa S, Desai R, Peng YQ, Matza D, Mehal WZ, Kaczmarek LK, Boulpaep EL, Flavell RA. Requirement of Voltage-Gated Calcium Channel ß4 Subunit for T Lymphocyte Functions. Science 2005, 307: 117-121. PMID: 15637280, DOI: 10.1126/science.1100582.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCalcium Channels, L-TypeCalcium SignalingCD4-Positive T-LymphocytesCytokinesDNA-Binding ProteinsIon Channel GatingLymphocyte ActivationMembrane PotentialsMiceMice, Inbred C3HMice, Inbred C57BLMutationNFATC Transcription FactorsNuclear ProteinsPatch-Clamp TechniquesPhosphorylationProtein SubunitsReceptors, Antigen, T-CellT-LymphocytesTranscription FactorsConceptsT lymphocytesCalcium channelsVoltage-gated calcium channelsT lymphocyte functionT cell receptor stimulationCell receptor stimulationCytokine productionLymphocyte functionCalcium influxReceptor stimulationCalcium responseCalcium entryTranscription factor NFATCav1 channelsLymphocytesAlpha1 subunitCav channelsNormal functionNonexcitable cellsDisplay impairmentsExcitable cellsChannel openingMolecular identityDiverse physiological processesPhysiological processes
2004
Exposure to Hypoxia Rapidly Induces Mitochondrial Channel Activity within a Living Synapse*
Jonas EA, Hickman JA, Hardwick JM, Kaczmarek LK. Exposure to Hypoxia Rapidly Induces Mitochondrial Channel Activity within a Living Synapse*. Journal Of Biological Chemistry 2004, 280: 4491-4497. PMID: 15561723, DOI: 10.1074/jbc.m410661200.Peer-Reviewed Original ResearchConceptsMitochondrial channel activityMitochondrial membraneChannel activityBcl-xLBcl-2 family proteinsPro-apoptotic fragmentsOuter mitochondrial membraneTrigger cell deathZ-VAD-FMKBenzyloxycarbonyl-VADFamily proteinsSynaptic responsesMulticonductance channelLarge conductance channelFluoromethyl ketoneCell deathMinutes of hypoxiaResponses of neuronsNeuronal functionSquid giant synapseSynaptic mitochondriaEarly eventsSynaptic functionHypoxic conditionsNeuronal deathActivation of a calcium entry pathway by sodium pyrithione in the bag cell neurons of Aplysia
Knox RJ, Magoski NS, Wing D, Barbee SJ, Kaczmarek LK. Activation of a calcium entry pathway by sodium pyrithione in the bag cell neurons of Aplysia. Developmental Neurobiology 2004, 60: 411-423. PMID: 15307146, DOI: 10.1002/neu.20029.Peer-Reviewed Original ResearchConceptsAplysia bag cell neuronsWhole-cell current-clamp recordingsBag cell neuronsPlasma membraneCurrent-clamp recordingsNeuronal physiologyCytosolic pHCytosolic freeMembrane potentialCell neuronsSodium pyrithionePresence of externalRatiometric imagingMV depolarizationClose structural analogueHill coefficientNapStructural analoguesSpeciesKv1.3 Channel Gene-Targeted Deletion Produces “Super-Smeller Mice” with Altered Glomeruli, Interacting Scaffolding Proteins, and Biophysics
Fadool DA, Tucker K, Perkins R, Fasciani G, Thompson RN, Parsons AD, Overton JM, Koni PA, Flavell RA, Kaczmarek LK. Kv1.3 Channel Gene-Targeted Deletion Produces “Super-Smeller Mice” with Altered Glomeruli, Interacting Scaffolding Proteins, and Biophysics. Neuron 2004, 41: 389-404. PMID: 14766178, PMCID: PMC2737549, DOI: 10.1016/s0896-6273(03)00844-4.Peer-Reviewed Original ResearchMeSH Keywords14-3-3 ProteinsAdaptor Proteins, Vesicular TransportAnimalsBehavior, AnimalBlotting, WesternBody WeightBrain-Derived Neurotrophic FactorCalcium ChannelsCells, CulturedDensitometryDifferential ThresholdDiscrimination, PsychologicalDose-Response Relationship, DrugDrinkingElectric StimulationEmbryo, MammalianEnergy IntakeExploratory BehaviorGene DeletionGRB10 Adaptor ProteinHabituation, PsychophysiologicHumansInsulinKidneyKineticsKv1.3 Potassium ChannelMembrane PotentialsMiceMice, KnockoutMotor ActivityNerve Tissue ProteinsNeuronsNeurotoxinsNuclear Matrix-Associated ProteinsOdorantsOlfactory BulbPatch-Clamp TechniquesPotassium ChannelsPotassium Channels, Voltage-GatedProteinsRas ProteinsReceptor, trkBReverse Transcriptase Polymerase Chain ReactionRNA, MessengerScorpion VenomsSensory ThresholdsSrc-Family KinasesTime FactorsTyrosine 3-MonooxygenaseConceptsKv1.3-/- miceProtein-protein interactionsGene-targeted deletionKv1.3-null miceSignal transductionScaffolding proteinSignaling cascadesChannel genesC-type inactivationDeletionMembrane potentialNull miceOlfactory codingDetection of odorsPotassium channelsKv1.3 channelsProteinSense of smellSlow inactivation kineticsWild-type miceTransductionGenesOlfactory bulb mitral cellsMiceRole
2003
Compensatory Anion Currents in Kv1.3 Channel-deficient Thymocytes*
Koni PA, Khanna R, Chang MC, Tang MD, Kaczmarek LK, Schlichter LC, Flavell R. Compensatory Anion Currents in Kv1.3 Channel-deficient Thymocytes*. Journal Of Biological Chemistry 2003, 278: 39443-39451. PMID: 12878608, DOI: 10.1074/jbc.m304879200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBase SequenceCell DivisionChloride ChannelsDNAFemaleGene ExpressionIon TransportKv1.3 Potassium ChannelLymphocyte ActivationMaleMembrane PotentialsMiceMice, Inbred C57BLMice, KnockoutPatch-Clamp TechniquesPotassium ChannelsPotassium Channels, Voltage-GatedRNA, MessengerT-LymphocytesConceptsWild-type cellsKv1.3-/- micePotassium channel subunitsVoltage-gated potassium channelsMouse thymocyte subsetsChloride currentsChannel subunitsAnion currentsT-cell activation/proliferationVoltage-dependent potassium currentsVolume regulationCell proliferationThymocyte apoptosisT cell responsesCell-mediated cytotoxicityObvious defectsCell activation/proliferationImmune system defectsT cell proliferationActivation/proliferationPotassium channelsLymph nodesCompensatory effectLymphocyte typeKv1.3