2024
Molecular Profiling of Mouse Models of Loss or Gain of Function of the KCNT1 (Slack) Potassium Channel and Antisense Oligonucleotide Treatment
Sun F, Wang H, Wu J, Quraishi I, Zhang Y, Pedram M, Gao B, Jonas E, Nguyen V, Wu S, Mabrouk O, Jafar-nejad P, Kaczmarek L. Molecular Profiling of Mouse Models of Loss or Gain of Function of the KCNT1 (Slack) Potassium Channel and Antisense Oligonucleotide Treatment. Biomolecules 2024, 14: 1397. PMID: 39595574, PMCID: PMC11591899, DOI: 10.3390/biom14111397.Peer-Reviewed Original ResearchWild-type miceKO miceSpectrum of epilepsy syndromesAntisense oligonucleotidesGain-of-function variantsAntisense oligonucleotide treatmentEpileptic phenotypePotassium channelsKCNT1Molecular profilingOligonucleotide treatmentAnimal modelsEpilepsy syndromesC-terminal mutationsIncreased expressionCerebral cortexMiceExpression of multiple proteinsComprehensive proteomic analysisDisease modelsCortical mitochondriaMolecular differencesDensity of mitochondrial cristaeMitochondrial membraneTreatment
2019
Modulators of Kv3 Potassium Channels Rescue the Auditory Function of Fragile X Mice
El-Hassar L, Song L, Tan WJT, Large CH, Alvaro G, Santos-Sacchi J, Kaczmarek LK. Modulators of Kv3 Potassium Channels Rescue the Auditory Function of Fragile X Mice. Journal Of Neuroscience 2019, 39: 4797-4813. PMID: 30936239, PMCID: PMC6561694, DOI: 10.1523/jneurosci.0839-18.2019.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAuditory PathwaysAuditory PerceptionBrain StemCochlear NucleusElectrophysiological PhenomenaEvoked Potentials, Auditory, Brain StemFemaleFragile X Mental Retardation ProteinFragile X SyndromeHydantoinsIn Vitro TechniquesMaleMiceMice, KnockoutPatch-Clamp TechniquesPyridinesShaw Potassium ChannelsConceptsAuditory brainstem responseWild-type animalsRepetitive firingABR wave ICurrent-clamp recordingsAuditory brainstem nucleiVoltage-clamp recordingsHigh-frequency firingSingle action potentialFragile X syndromeTrapezoid bodyBrainstem nucleiBrainstem responseMedial nucleusAuditory brainstemAuditory nerveWave IWave IVAction potentialsSensory stimuliKv3.1 channelsCentral processingMental retardation proteinHigh sound levelsMice
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
2004
Kv1.3 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
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 roleExcitabilityThe voltage-gated potassium channel Kv1.3 regulates energy homeostasis and body weight
Xu J, Koni PA, Wang P, Li G, Kaczmarek L, Wu Y, Li Y, Flavell RA, Desir GV. The voltage-gated potassium channel Kv1.3 regulates energy homeostasis and body weight. Human Molecular Genetics 2003, 12: 551-559. PMID: 12588802, DOI: 10.1093/hmg/ddg049.Peer-Reviewed Original ResearchConceptsBody weightBasal metabolic rateKv1.3 channelsDiet-induced obesityHigh-fat dietBody weight regulationT cell activationVoltage-gated potassium channel Kv1.3Voltage-gated potassium channelsPotassium channel Kv1.3Control littermatesFood intakeLittermate controlsKnockout miceWeight regulationIndirect calorimetryMetabolic rateChannel inhibitionCell activationEnergy homeostasisKnockout animalsPotassium channelsCell membrane potentialMiceChannel Kv1.3
2001
Adhesion Molecules and Axon Pathfinding
B.Levitan I, Kaczmarek L. Adhesion Molecules and Axon Pathfinding. 2001, 435-466. DOI: 10.1093/oso/9780195145236.003.0017.Peer-Reviewed Original ResearchNervous systemNeuronal activityDendritic branchesSuperior cervical ganglionDendritic branching patternsMature nervous systemTypes of synapsesIntact nervous systemCervical ganglionLong-term regulationSynaptic connectionsIntact animalsNeuronal structuresAdhesion moleculesNeuronsElectrical activityGangliaFluorescent cellsBranching patternDendritesCellsSpecific patternsAxonsMiceActivity