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
2021
A KCNC1 mutation in epilepsy of infancy with focal migrating seizures produces functional channels that fail to be regulated by PKC phosphorylation
Zhang Y, Ali SR, Nabbout R, Barcia G, Kaczmarek LK. A KCNC1 mutation in epilepsy of infancy with focal migrating seizures produces functional channels that fail to be regulated by PKC phosphorylation. Journal Of Neurophysiology 2021, 126: 532-539. PMID: 34232791, PMCID: PMC8409950, DOI: 10.1152/jn.00257.2021.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCHO CellsCricetinaeCricetulusEpilepsyMutationPhosphorylationProtein Kinase CShaw Potassium ChannelsSialyltransferasesConceptsFunctional channelsProtein kinase C.Serious human diseasesPotassium channelsWild-type channelsEpilepsy of infancyChannel modulationTerminal domainIon channel mutationsPKC phosphorylationC-terminusNormal neuronal functionChannel proteinsKv3.1 potassium channelRegulatory sitesKinase C.Human diseasesChannel functionPhosphorylationIon channelsMutationsNovo variantsChannel mutationsBiophysical propertiesNeuronal function
2016
Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia
Onorati M, Li Z, Liu F, Sousa AMM, Nakagawa N, Li M, Dell’Anno M, Gulden FO, Pochareddy S, Tebbenkamp AT, Han W, Pletikos M, Gao T, Zhu Y, Bichsel C, Varela L, Szigeti-Buck K, Lisgo S, Zhang Y, Testen A, Gao XB, Mlakar J, Popovic M, Flamand M, Strittmatter SM, Kaczmarek LK, Anton ES, Horvath TL, Lindenbach BD, Sestan N. Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia. Cell Reports 2016, 16: 2576-2592. PMID: 27568284, PMCID: PMC5135012, DOI: 10.1016/j.celrep.2016.08.038.Peer-Reviewed Original ResearchMeSH KeywordsAxl Receptor Tyrosine KinaseBrainCell DeathCentrosomeFetusGene Expression ProfilingHumansImmunity, InnateMicrocephalyMitochondriaMitosisNeocortexNeural Stem CellsNeuroepithelial CellsNeurogliaNeuronsNeuroprotective AgentsNucleosidesPhosphorylationProtein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesSpinal CordTranscription, GeneticVirus ReplicationZika VirusZika Virus InfectionConceptsRadial glial cellsNES cellsNeuroepithelial stem cellsZIKV infectionFetal brain slicesStem cellsEarly human neurodevelopmentHuman neuroepithelial stem cellsHuman neural stem cellsCell deathSingle-cell RNA-seqNeural stem cellsNeurodevelopment defectsZIKV replicationGlial cellsBrain slicesPotential treatmentRadial gliaZika virusPhospho-TBK1Neurodevelopmental defectsRNA-seqSupernumerary centrosomesNucleoside analoguesHuman neurodevelopmentStimulation 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
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 ResearchConceptsEffect 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 analysisDe novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy
Barcia G, Fleming MR, Deligniere A, Gazula VR, Brown MR, Langouet M, Chen H, Kronengold J, Abhyankar A, Cilio R, Nitschke P, Kaminska A, Boddaert N, Casanova JL, Desguerre I, Munnich A, Dulac O, Kaczmarek LK, Colleaux L, Nabbout R. De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy. Nature Genetics 2012, 44: 1255-1259. PMID: 23086397, PMCID: PMC3687547, DOI: 10.1038/ng.2441.Peer-Reviewed Original Research
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
2008
Protein Kinase C Modulates Inactivation of Kv3.3 Channels*
Desai R, Kronengold J, Mei J, Forman SA, Kaczmarek LK. Protein Kinase C Modulates Inactivation of Kv3.3 Channels*. Journal Of Biological Chemistry 2008, 283: 22283-22294. PMID: 18539595, PMCID: PMC2494927, DOI: 10.1074/jbc.m801663200.Peer-Reviewed Original Research
2006
Modulation of Kv3.1b Potassium Channel Phosphorylation in Auditory Neurons by Conventional and Novel Protein Kinase C Isozymes*
Song P, Kaczmarek LK. Modulation of Kv3.1b Potassium Channel Phosphorylation in Auditory Neurons by Conventional and Novel Protein Kinase C Isozymes*. Journal Of Biological Chemistry 2006, 281: 15582-15591. PMID: 16595659, DOI: 10.1074/jbc.m512866200.Peer-Reviewed Original ResearchConceptsAuditory neuronsMNTB neuronsTrapezoid bodyBrief high-frequency electrical stimulationProtein kinase CMetabotropic glutamate receptor activationHigh-frequency electrical stimulationBasal phosphorylationGlutamate receptor activationHigh-frequency stimulationFrequency electrical stimulationHigh-frequency firingMature nervous systemKv3.1 potassium channelNeuronal abilityBrainstem slicesMedial nucleusFrequency stimulationAuditory brainstemFrequency firingConventional protein kinase CPharmacological activationNervous systemElectrical stimulationPKC isozymes
2005
Acoustic environment determines phosphorylation state of the Kv3.1 potassium channel in auditory neurons
Song P, Yang Y, Barnes-Davies M, Bhattacharjee A, Hamann M, Forsythe ID, Oliver DL, Kaczmarek LK. Acoustic environment determines phosphorylation state of the Kv3.1 potassium channel in auditory neurons. Nature Neuroscience 2005, 8: 1335-1342. PMID: 16136041, DOI: 10.1038/nn1533.Peer-Reviewed Original ResearchMeSH KeywordsAcoustic StimulationAction PotentialsAnimalsAnimals, NewbornBrain StemCHO CellsCricetinaeCricetulusDose-Response Relationship, RadiationElectric StimulationEnzyme InhibitorsFunctional LateralityGene Expression RegulationImmunohistochemistryIn Vitro TechniquesIndolesMaleimidesNeuronsPatch-Clamp TechniquesPhosphorylationProtein Kinase CRatsRats, Sprague-DawleyTetradecanoylphorbol AcetateConceptsKv3.1 potassium channelAction potentialsAuditory neuronsPotassium channelsShort-duration action potentialsRat brainstem neuronsAuditory brainstem nucleiProtein kinase CHigh-frequency spikingHigh-frequency auditoryBrainstem neuronsHigh-frequency stimuliBrainstem nucleiSynaptic stimulationNeuronsInteraural differencesSound localizationIntrinsic electrical propertiesKinase CRegulation of the timing of MNTB neurons by short-term and long-term modulation of potassium channels
Kaczmarek LK, Bhattacharjee A, Desai R, Gan L, Song P, von Hehn CA, Whim MD, Yang B. Regulation of the timing of MNTB neurons by short-term and long-term modulation of potassium channels. Hearing Research 2005, 206: 133-145. PMID: 16081004, DOI: 10.1016/j.heares.2004.11.023.Peer-Reviewed Original ResearchConceptsAnteroventral cochlear nucleusPotassium channelsAuditory pathwayAction potentialsCentral auditory pathwayVoltage-dependent potassium channelsMammalian auditory pathwayAmount of neurotransmitterProtein phosphorylationMNTB neuronsGene expressionBushy cellsPrincipal neuronsTrapezoid bodyCochlear nucleusIntrinsic excitabilityMedial nucleusVoltage-dependent channelsFiring patternsNeuronsAmplitude of currentsKv1 familySound stimuliLong-term modulationSound localizationRequirement 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
Loss of Kv3.1 Tonotopicity and Alterations in cAMP Response Element-Binding Protein Signaling in Central Auditory Neurons of Hearing Impaired Mice
von Hehn CA, Bhattacharjee A, Kaczmarek LK. Loss of Kv3.1 Tonotopicity and Alterations in cAMP Response Element-Binding Protein Signaling in Central Auditory Neurons of Hearing Impaired Mice. Journal Of Neuroscience 2004, 24: 1936-1940. PMID: 14985434, PMCID: PMC6730406, DOI: 10.1523/jneurosci.4554-03.2004.Peer-Reviewed Original ResearchMeSH KeywordsAcoustic StimulationAge FactorsAnimalsAuditory PathwaysBrain StemCerebellumCyclic AMP Response Element-Binding ProteinDisease ProgressionMaleMiceMice, Inbred C57BLMice, Inbred CBAMice, Inbred DBANeuronsNeuropeptidesPhosphorylationPotassium ChannelsPotassium Channels, Voltage-GatedPresbycusisReflex, StartleShaw Potassium ChannelsConceptsCAMP response element-binding proteinResponse element-binding proteinTonotopic axisBL/6 miceElement-binding proteinCochlear hair cell lossPCREB-positive cellsAuditory brainstem neuronsCentral auditory neuronsHair cell lossCBA/JTranscription factor cAMP response element-binding proteinBrainstem neuronsKv3.1 potassium channel geneTrapezoid bodyImpaired miceMedial nucleusAuditory brainstemImmunopositive cellsAuditory neuronsMedial endPotassium channel genesGood hearingCell lossCREB expression
2003
Modulation of the Kv3.1b Potassium Channel Isoform Adjusts the Fidelity of the Firing Pattern of Auditory Neurons
Macica CM, von Hehn CA, Wang LY, Ho CS, Yokoyama S, Joho RH, Kaczmarek LK. Modulation of the Kv3.1b Potassium Channel Isoform Adjusts the Fidelity of the Firing Pattern of Auditory Neurons. Journal Of Neuroscience 2003, 23: 1133-1141. PMID: 12598601, PMCID: PMC6742259, DOI: 10.1523/jneurosci.23-04-01133.2003.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsBrain StemCells, CulturedCHO CellsCricetinaeElectric ConductivityEvoked Potentials, AuditoryKineticsMiceMice, KnockoutNeuronsNeuropeptidesPatch-Clamp TechniquesPhosphorylationPotassium ChannelsPotassium Channels, Voltage-GatedProtein IsoformsProtein Kinase CSerineShaw Potassium ChannelsTetradecanoylphorbol AcetateConceptsTrapezoid bodyMedial nucleusAuditory neuronsHigh-frequency stimulationWild-type neuronsKv3.1 potassium channelHigh-threshold componentPotassium channel isoformsGreat temporal precisionPartial decreaseProtein kinase C activationAction potentialsLocation of soundsMice resultsFiring patternsNeuronsSensory stimulationPotassium channelsChannel isoformsKinase C activationKv3.1Kv3.1 geneStimulationHigh frequencyProtein kinase C
2002
Protein Kinase Modulation of a Neuronal Cation Channel Requires Protein–Protein Interactions Mediated by an Src homology 3 Domain
Magoski NS, Wilson GF, Kaczmarek LK. Protein Kinase Modulation of a Neuronal Cation Channel Requires Protein–Protein Interactions Mediated by an Src homology 3 Domain. Journal Of Neuroscience 2002, 22: 1-9. PMID: 11756482, PMCID: PMC6757624, DOI: 10.1523/jneurosci.22-01-00001.2002.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAmino Acid MotifsAmino Acid SequenceAnimalsAplysiaCationsCells, CulturedIon Channel GatingIon ChannelsMacromolecular SubstancesMembrane PotentialsMolecular Sequence DataMultiprotein ComplexesNeuronsPatch-Clamp TechniquesPeptidesPhosphorylationProtein BindingProtein Kinase CSrc Homology DomainsConceptsProtein-protein interactionsSrc homology 3 domainProtein kinase CSH3 domainSH3 domain-mediated interactionsDomain-mediated interactionsIon channelsSrc SH3 domainProtein kinase modulationMultiprotein complexesPDZ domainAdaptor proteinProtein kinaseKinase modulationIon channel modulationKinase CMotif peptideCation channel activationKinaseChannel open probabilityCation channelsMembrane depolarizationChannel activationChannel modulationProtein
2001
Casein Kinase 2 Determines the Voltage Dependence of the Kv3.1 Channel in Auditory Neurons and Transfected Cells
Macica C, Kaczmarek L. Casein Kinase 2 Determines the Voltage Dependence of the Kv3.1 Channel in Auditory Neurons and Transfected Cells. Journal Of Neuroscience 2001, 21: 1160-1168. PMID: 11160386, PMCID: PMC6762230, DOI: 10.1523/jneurosci.21-04-01160.2001.Peer-Reviewed Original ResearchMeSH KeywordsAlkaline PhosphataseAnimalsAuditory PathwaysBinding SitesBrain StemCasein Kinase IICDC2-CDC28 KinasesCHO CellsCricetinaeCyclin-Dependent Kinase 2Cyclin-Dependent KinasesElectric StimulationEnzyme InhibitorsIn Vitro TechniquesMembrane PotentialsNeuronsNeuropeptidesPatch-Clamp TechniquesPhosphorylationPotassium ChannelsPotassium Channels, Voltage-GatedPrecipitin TestsProtein Kinase CProtein Serine-Threonine KinasesRatsShaw Potassium ChannelsTetradecanoylphorbol AcetateTransfectionConceptsCasein kinase 2Kinase 2Casein kinase IIProtein kinase CKv3.1 channelsChinese hamster ovary cellsHamster ovary cellsConstitutive phosphorylationPhosphatase treatmentKinase IIKinase CTransfected CellsVoltage-dependent activationOvary cellsWhole-cell conductancePhosphorylationPotassium channelsRectifier channelsBiophysical characteristicsInactivationKv3.1 potassium channelVoltage dependenceActivationKv3.1Patch-clamp recordings
1996
Regulation 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 StatementsMeSH KeywordsAnimalsCell MembraneEnzyme ActivationHumansKineticsPhosphorylationPotassium ChannelsProtein KinasesSerineThreonineTyrosine
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
1992
Modulation by cAMP of a slowly activating potassium channel expressed in Xenopus oocytes
Blumenthal E, Kaczmarek L. Modulation by cAMP of a slowly activating potassium channel expressed in Xenopus oocytes. Journal Of Neuroscience 1992, 12: 290-296. PMID: 1370322, PMCID: PMC6575684, DOI: 10.1523/jneurosci.12-01-00290.1992.Peer-Reviewed Original ResearchMeSH Keywords8-Bromo Cyclic Adenosine MonophosphateAmino Acid SequenceAnimalsCell MembraneCyclic AMPFemaleGene ExpressionHumansMembrane PotentialsMembrane ProteinsMolecular Sequence DataMutagenesis, Site-DirectedOocytesPhosphorylationPotassium ChannelsPotassium Channels, Voltage-GatedProgesteroneProtein Kinase InhibitorsProtein KinasesRatsRNATransfectionXenopus laevisConceptsMinK proteinCAMP-dependent protein kinasePotential phosphorylation sitesXenopus oocytesCAMP levelsPhosphorylation sitesProtein kinasePlasma membraneKinase activityChannel proteinsIntracellular cAMP levelsProtein inhibitorProteinKinasePotassium channelsOocytesVoltage-dependent potassium currentsIsK
1991
Phosphorylation of membrane‐associated proteins by phorbol esters in isolated bag cell neurons of Aplysia
Azhderian E, Kaczmarek L. Phosphorylation of membrane‐associated proteins by phorbol esters in isolated bag cell neurons of Aplysia. Developmental Neurobiology 1991, 22: 105-115. PMID: 2030336, DOI: 10.1002/neu.480220202.Peer-Reviewed Original ResearchConceptsProtein kinase CBag cell neuronsKinase CPlasma membrane-containing fractionsProtein kinase C inhibitor H7Membrane-associated proteinsPhorbol esterExtent of phosphorylationMembrane-containing fractionsCell neuronsMembrane proteinsProtein phosphorylationNew speciesPhosphorylation statePlasma membraneTetradecanoyl phorbol 13Inhibitor H7Inactive phorbol esterIntact cellsPhosphate incorporationProtein extractsPhosphoproteinExtracellular mediumPhosphorylationProtein