2021
Suppression of Kv3.3 channels by antisense oligonucleotides reverses biochemical effects and motor impairment in spinocerebellar ataxia type 13 mice
Zhang Y, Quraishi IH, McClure H, Williams LA, Cheng Y, Kale S, Dempsey GT, Agrawal S, Gerber DJ, McManus OB, Kaczmarek LK. Suppression of Kv3.3 channels by antisense oligonucleotides reverses biochemical effects and motor impairment in spinocerebellar ataxia type 13 mice. The FASEB Journal 2021, 35: e22053. PMID: 34820911, PMCID: PMC8630780, DOI: 10.1096/fj.202101356r.Peer-Reviewed Original ResearchConceptsHAX-1Wild-type animalsMultivesicular bodiesKv3.3 channelsLate endosomes/multivesicular bodiesTank Binding Kinase 1Type animalsCell survival proteinsDisease-causing mutationsVoltage-dependent potassium channelsSpinocerebellar ataxia type 13Survival proteinsKinase 1Mature intact animalsTBK1 activationAge-matched wild-type animalsLevels of CD63Progressive cerebellar degenerationWild-type miceMutationsProtein levelsMutant micePotassium channelsDependent potassium channelsType mice
2020
Impaired motor skill learning and altered seizure susceptibility in mice with loss or gain of function of the Kcnt1 gene encoding Slack (KNa1.1) Na+-activated K+ channels
Quraishi IH, Mercier MR, McClure H, Couture RL, Schwartz ML, Lukowski R, Ruth P, Kaczmarek LK. Impaired motor skill learning and altered seizure susceptibility in mice with loss or gain of function of the Kcnt1 gene encoding Slack (KNa1.1) Na+-activated K+ channels. Scientific Reports 2020, 10: 3213. PMID: 32081855, PMCID: PMC7035262, DOI: 10.1038/s41598-020-60028-z.Peer-Reviewed Original ResearchConceptsMaximum electroshock-induced seizuresEpilepsy of infancyPentylenetetrazole-induced seizuresVideo-EEG monitoringElectroshock-induced seizuresForms of epilepsyWild-type miceSlack channelsImpaired motor skillsProcedural motor learningMotor skillsWild-type animalsSevere intellectual disabilityOpen-field behaviorCortical seizuresKCNT1 geneSpontaneous seizuresFocal seizuresSeizure susceptibilitySeizure activityType miceMouse modelAnimal modelsInterictal spikesSeizures
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
2013
The contribution of TWIK-1 channels to astrocyte K+ current is limited by retention in intracellular compartments
Wang W, Putra A, Schools GP, Ma B, Chen H, Kaczmarek LK, Barhanin J, Lesage F, Zhou M. The contribution of TWIK-1 channels to astrocyte K+ current is limited by retention in intracellular compartments. Frontiers In Cellular Neuroscience 2013, 7: 246. PMID: 24368895, PMCID: PMC3856854, DOI: 10.3389/fncel.2013.00246.Peer-Reviewed Original ResearchTWIK-1 channelsTWIK-1Plasma membraneIntracellular compartmentsMature hippocampal astrocytesTwo-pore domainWild-type animalsFractionation experimentsTwo-poreKnockout miceCytoplasmic fractionExpression of Kir4.1Compartment fractionsType animalsPhysiological conditionsTREK-1Whole-cell currentsLow-level presenceKnockoutLinear current-voltage relationshipCompartmentsMembraneMild effect
2010
Fragile X Mental Retardation Protein Is Required for Rapid Experience-Dependent Regulation of the Potassium Channel Kv3.1b
Strumbos JG, Brown MR, Kronengold J, Polley DB, Kaczmarek LK. Fragile X Mental Retardation Protein Is Required for Rapid Experience-Dependent Regulation of the Potassium Channel Kv3.1b. Journal Of Neuroscience 2010, 30: 10263-10271. PMID: 20685971, PMCID: PMC3485078, DOI: 10.1523/jneurosci.1125-10.2010.Peer-Reviewed Original ResearchConceptsMental retardation proteinAnterior ventral cochlear nucleusFragile X Mental Retardation ProteinRNA-binding proteinProtein translationFMRPWild-type animalsSpecific mRNAsSound localization circuitVentral cochlear nucleusBrainstem synaptosomesExperience-dependent regulationProtein levelsAmplitude-modulated stimuliProteinTrapezoid bodyCochlear nucleusMale miceMedial nucleusNeuronal activityPotassium currentWT controlsSynaptic plasticityTonotopic axisAcoustic stimulation