2024
Disease-causing Slack potassium channel mutations produce opposite effects on excitability of excitatory and inhibitory neurons
Wu J, Quraishi I, Zhang Y, Bromwich M, Kaczmarek L. Disease-causing Slack potassium channel mutations produce opposite effects on excitability of excitatory and inhibitory neurons. Cell Reports 2024, 43: 113904. PMID: 38457342, PMCID: PMC11013952, DOI: 10.1016/j.celrep.2024.113904.Peer-Reviewed Original ResearchInhibitory neuronsRegulation of neuronal excitabilityPotassium channel mutationsVoltage-dependent sodiumInhibitory cortical neuronsGain-of-function mutationsAxon initial segmentKCNT1 geneNeuronal excitabilityChannel subunitsChannel mutationsNetwork hyperexcitabilityMouse modelNeuron typesCortical neuronsTreat epilepsyNeuronsExcitable neuronsNeurological disordersSevere intellectual disabilityMutationsInitial segmentKCNT1ExpressionHyperexcitability
2022
Atrial AMP-activated protein kinase is critical for prevention of dysregulation of electrical excitability and atrial fibrillation
Su KN, Ma Y, Cacheux M, Ilkan Z, Raad N, Muller GK, Wu X, Guerrera N, Thorn SL, Sinusas AJ, Foretz M, Viollet B, Akar JG, Akar FG, Young LH. Atrial AMP-activated protein kinase is critical for prevention of dysregulation of electrical excitability and atrial fibrillation. JCI Insight 2022, 7: e141213. PMID: 35451373, PMCID: PMC9089788, DOI: 10.1172/jci.insight.141213.Peer-Reviewed Original ResearchConceptsTranscription factorsKey transcription factorMaster metabolic regulatorIon channel subunitsGap junction proteinTranscriptional reprogrammingAMPK deletionProtein kinaseBiological functionsTranscriptional downregulationMetabolic regulatorChannel subunitsIon channelsAMPK expressionMetabolic stressAtrial fibrillationAMPKJunction proteinsElectrical excitabilityHomeostatic roleStructural remodelingConnexinsAtrial ion channelsRemodelingDownregulation
2018
Extraction of Auditory Information by Modulation of Neuronal Ion Channels
Kaczmarek L. Extraction of Auditory Information by Modulation of Neuronal Ion Channels. 2018, 273-300. DOI: 10.1093/oxfordhb/9780190849061.013.23.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsTrapezoid bodyMedial nucleusNeuronal firing patternsGroups of neuronsPotassium channel subunitsAuditory neuronsFiring patternsChannel subunitsAuditory informationIon channelsAuditory inputNeuronal ion channelsSuch modulationComplex soundsSpecific patternsNeuronsIncoming stimuliAuditory environmentIdentical neuronsSame patternVariety of responsesSmall numberModulationReviewGroup
2015
Epilepsy-causing mutations in Kv7.2 C-terminus affect binding and functional modulation by calmodulin
Ambrosino P, Alaimo A, Bartollino S, Manocchio L, De Maria M, Mosca I, Gomis-Perez C, Alberdi A, Scambia G, Lesca G, Villarroel A, Taglialatela M, Soldovieri MV. Epilepsy-causing mutations in Kv7.2 C-terminus affect binding and functional modulation by calmodulin. Biochimica Et Biophysica Acta 2015, 1852: 1856-1866. PMID: 26073431, DOI: 10.1016/j.bbadis.2015.06.012.Peer-Reviewed Original ResearchBenign familial neonatal seizuresKv7.2/Kv7.3 channelsFunctional modulationPatch-clamp recordingsPotential therapeutic approachFamilial neonatal seizuresComplete functional lossNeonatal seizuresEpileptic encephalopathyPathogenetic mechanismsTherapeutic approachesChannel dysfunctionCaM affinityEpilepsy-causing mutationsKv7.3 channelsFunctional lossCaM overexpressionFunctional changesEpileptic diseasePhenotypic presentationChannel subunitsKCNQ2 geneKv7.2Significant alterationsC-terminal fragment
2010
Specific and rapid effects of acoustic stimulation on the tonotopic distribution of Kv3.1b potassium channels in the adult rat
Strumbos J, Polley D, Kaczmarek L. Specific and rapid effects of acoustic stimulation on the tonotopic distribution of Kv3.1b potassium channels in the adult rat. Neuroscience 2010, 167: 567-572. PMID: 20219640, PMCID: PMC2854512, DOI: 10.1016/j.neuroscience.2010.02.046.Peer-Reviewed Original ResearchMeSH KeywordsAcoustic StimulationAdaptation, PhysiologicalAnimalsAntibody SpecificityAuditory PathwaysAuditory ThresholdImmunohistochemistryIon Channel GatingNerve Tissue ProteinsNeuronal PlasticityRatsRats, Sprague-DawleyReaction TimeRhombencephalonShaw Potassium ChannelsSound LocalizationSynaptic TransmissionTime FactorsUp-RegulationConceptsTotal cellular levelsCytoplasmic C-terminusCellular levelVoltage-gated potassium channel subunitsPotassium channel subunitsTonotopic distributionAdult ratsC-terminusChannel proteinsChannel subunitsSound localization circuitIon channelsProteinExperience-dependent plasticityCultured neuronsPotassium channelsHigh-frequency stimuliAcute slicesMedial nucleusSynaptic activityAuditory neuronsKv3.1 proteinMin of exposureAction potentialsAcoustic stimulation
2007
A Specific Subset of Transient Receptor Potential Vanilloid-Type Channel Subunits in Caenorhabditis elegans Endocrine Cells Function as Mixed Heteromers to Promote Neurotransmitter Release
Jose AM, Bany IA, Chase DL, Koelle MR. A Specific Subset of Transient Receptor Potential Vanilloid-Type Channel Subunits in Caenorhabditis elegans Endocrine Cells Function as Mixed Heteromers to Promote Neurotransmitter Release. Genetics 2007, 175: 93-105. PMID: 17057248, PMCID: PMC1774992, DOI: 10.1534/genetics.106.065516.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAnimals, Genetically ModifiedBiological TransportCaenorhabditis elegansCaenorhabditis elegans ProteinsEndocrine GlandsFemaleIon ChannelsMolecular Sequence DataNerve Tissue ProteinsNeurosecretory SystemsOvipositionSequence Homology, Amino AcidTRPV Cation ChannelsConceptsOCR-2Neuroendocrine cellsEgg-laying defectsTRPV channel OSM-9Heteromeric channelsG protein GDominant negative mutantTransient receptor potential channelsEndocrine cell functionOSM-9Heteromeric partnerTRPV channelsSensory neuronsSingle knockoutDetectable functionOCR-1Premature eggsSensory transductionChannel subunitsDetectable roleSubunit compositionCell functionRelease of neurotransmittersNeurotransmitter releaseSubunit combinations
2006
Pharmacological 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 patchesPolicing 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 Research
2005
Dissection of synaptic excitability phenotypes by using a dominant-negative Shaker K+ channel subunit
Mosca TJ, Carrillo RA, White BH, Keshishian H. Dissection of synaptic excitability phenotypes by using a dominant-negative Shaker K+ channel subunit. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 3477-3482. PMID: 15728380, PMCID: PMC552910, DOI: 10.1073/pnas.0406164102.Peer-Reviewed Original ResearchConceptsNeuromuscular junctionPostsynaptic membrane excitabilityChannel subunitsActivity-dependent changesPotassium channel subunitsPostsynaptic potentialsNervous system developmentNeuronal excitabilityArbor growthIA currentsPostsynaptic partnersArbor sizeNeurotransmitter releaseMembrane excitabilityLarval neuromuscular junctionElectrical excitabilityExcitabilityElectrical activityBehavioral phenotypesMuscleSh mutationsMorphological changesPhenotypeMotoneuronsNeurons
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 typeKv1.3Serum- and Glucocorticoid-Regulated Kinase Isoform-1 and Epithelial Sodium Channel Subunits in Human Ocular Ciliary Epithelium
Rauz S, Walker EA, Hughes SV, Coca-Prados M, Hewison M, Murray PI, Stewart PM. Serum- and Glucocorticoid-Regulated Kinase Isoform-1 and Epithelial Sodium Channel Subunits in Human Ocular Ciliary Epithelium. Investigative Ophthalmology & Visual Science 2003, 44: 1643-1651. PMID: 12657604, DOI: 10.1167/iovs.02-0514.Peer-Reviewed Original ResearchMeSH KeywordsAldosteroneBlotting, NorthernCell LineCiliary BodyDexamethasoneDose-Response Relationship, DrugDrug CombinationsEpithelial Sodium ChannelsGene Expression RegulationGlucocorticoidsHormone AntagonistsHumansImmediate-Early ProteinsIn Situ HybridizationIsoenzymesMifepristoneMineralocorticoid Receptor AntagonistsNuclear ProteinsPigment Epithelium of EyeProtein Serine-Threonine KinasesReceptors, GlucocorticoidReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSodium ChannelsSpironolactoneConceptsExpression of SGK1Human ocular ciliary epitheliumODM-2 cellsOcular ciliary epitheliumSodium transportCiliary epitheliumENaC subunitsNPE cell linesEpithelial sodium channel (ENaC) subunitsAqueous humor productionSodium channel subunitsExpression of ENaCRadioligand-binding assaysDose-dependent inductionIsoform 1Epithelial sodium channelCorticosteroid regulationHuman ocularAldosteroneCiliary epithelial bilayerRU26752DexamethasoneRT-PCR analysisSodium channelsChannel subunits
2002
Localization of the Slack potassium channel in the rat central nervous system
Bhattacharjee A, Gan L, Kaczmarek LK. Localization of the Slack potassium channel in the rat central nervous system. The Journal Of Comparative Neurology 2002, 454: 241-254. PMID: 12442315, DOI: 10.1002/cne.10439.Peer-Reviewed Original ResearchConceptsRat central nervous systemSlack potassium channelsChannel subunitsRat brain slicesCentral nervous systemRat brain membranesOnly cortical regionDeep cerebellar nucleiGiant presynaptic terminalSlo subunitWestern blot analysisSubstantia nigraTrigeminal systemImmunohistochemical studyMedial nucleusOculomotor nucleusReticular formationBrain slicesFrontal cortexOlfactory bulbPresynaptic terminalsRed nucleusNervous systemCerebellar nucleiBrain membranes
2000
Modification of delayed rectifier potassium currents by the Kv9.1 potassium channel subunit
Richardson F, Kaczmarek L. Modification of delayed rectifier potassium currents by the Kv9.1 potassium channel subunit. Hearing Research 2000, 147: 21-30. PMID: 10962170, DOI: 10.1016/s0378-5955(00)00117-9.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAuditory PathwaysComputer SimulationDelayed Rectifier Potassium ChannelsEvoked Potentials, AuditoryFemaleHumansIn Vitro TechniquesMembrane PotentialsModels, NeurologicalNeuronsOocytesPotassium ChannelsPotassium Channels, Voltage-GatedRatsRecombinant ProteinsShab Potassium ChannelsXenopus laevisConceptsRectifier potassium currentPotassium channel subunitsChannel subunitsPotassium currentInward currentsInhibition of firingHigh-frequency stimulationVariety of neuronsPotassium channel alpha subunitChannel alpha subunitFrequency stimulationAuditory pathwayInferior colliculusSustained depolarizationAction potentialsModel neuronsFiring patternsKv9.1NeuronsPotassium channelsAmplitude of currentsKv2.1Sound stimuliRate of activationTetraethyl ammonium ions
1999
Isolation of Receptor Clones by Expression Screening in Xenopus Oocytes
Nakamura F, Goshima Y, Strittmatter S, Kawamoto S. Isolation of Receptor Clones by Expression Screening in Xenopus Oocytes. Methods In Molecular Biology 1999, 128: 1-18. PMID: 10320969, DOI: 10.1385/1-59259-683-5:1.Peer-Reviewed Original Research
1998
Depolarization Selectively Increases the Expression of the Kv3.1 Potassium Channel in Developing Inferior Colliculus Neurons
Liu S, Kaczmarek L. Depolarization Selectively Increases the Expression of the Kv3.1 Potassium Channel in Developing Inferior Colliculus Neurons. Journal Of Neuroscience 1998, 18: 8758-8769. PMID: 9786983, PMCID: PMC6793528, DOI: 10.1523/jneurosci.18-21-08758.1998.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsAnimals, NewbornCalciumGene Expression Regulation, DevelopmentalIn Vitro TechniquesInferior ColliculiMembrane PotentialsNeuropeptidesPatch-Clamp TechniquesPotassiumPotassium ChannelsPotassium Channels, Voltage-GatedRatsRats, Sprague-DawleyRNA, MessengerShaw Potassium ChannelsConceptsInferior colliculus neuronsOnset of hearingColliculus neuronsCalcium influxChannel subunitsPotassium currentAction potentialsElevated external potassium concentrationCalcium channel blockersDepolarization-induced increaseSpontaneous neuronal activityNoninactivating potassium currentKv3.1 potassium channelVoltage-clamp experimentsChannel blockersNeuronal excitabilityElevated potassiumAuditory neuronsNeuronal activityExternal potassium concentrationExternal potassium ionsNeuronsPotassium channelsMRNA levelsMarked increaseFormation of intermediate-conductance calcium-activated potassium channels by interaction of Slack and Slo subunits
Joiner W, Tang M, Wang L, Dworetzky S, Boissard C, Gan L, Gribkoff V, Kaczmarek L. Formation of intermediate-conductance calcium-activated potassium channels by interaction of Slack and Slo subunits. Nature Neuroscience 1998, 1: 462-469. PMID: 10196543, DOI: 10.1038/2176.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsElectric ConductivityIntermediate-Conductance Calcium-Activated Potassium ChannelsIsomerismLarge-Conductance Calcium-Activated Potassium ChannelsMolecular Sequence DataNerve Tissue ProteinsPotassium ChannelsPotassium Channels, Calcium-ActivatedPotassium Channels, Sodium-ActivatedConceptsCalcium-activated potassium channelsIntracellular calciumNervous systemIntermediate-conductance calcium-activated potassium channelsPotassium channelsLarge-conductance calcium-activated potassium channelsControl of excitabilitySlo subunitIntermediate conductance channelPotassium channel genesPharmacological propertiesIntermediate conductanceCytoplasmic calciumChannel subunitsSlo channelsSlack channelsChannel genesSingle-channel conductanceUnitary conductanceCalciumExcitabilitySLOSecretion
1997
Downregulation of Na+ channel mRNA in olfactory bulb tufted cells following deafferentiation
Sashihara S, Waxman S, Greer C. Downregulation of Na+ channel mRNA in olfactory bulb tufted cells following deafferentiation. Neuroreport 1997, 8: 1289-1293. PMID: 9175131, DOI: 10.1097/00001756-199703240-00046.Peer-Reviewed Original ResearchConceptsOlfactory bulbMitral cellsEffects of deafferentationPostnatal day 2Olfactory receptor cellsFunctional deafferentationAfferent inputChannel expressionDay 2Channel mRNAReceptor cellsChannel subunitsDeafferentationI mRNACauterizationCritical periodDetectable changeAlpha IIOdorant accessSitu hybridizationCellsCell propertiesExpressionBulbMRNA
1995
Expression of sodium channel α- and β-subunits in the nervous system of themyelin-deficient rat
Felts P, Black J, Waxman S. Expression of sodium channel α- and β-subunits in the nervous system of themyelin-deficient rat. Brain Cell Biology 1995, 24: 654-666. PMID: 7500121, DOI: 10.1007/bf01179816.Peer-Reviewed Original ResearchConceptsSodium channel αMale littermatesSubtype-specific riboprobesDorsal root gangliaChannel αNormal male littermatesSodium channel subunitsUnaffected male littermatesDays of ageAdult expression patternRoot gangliaSpinal cordExpression patternsAdult ratsNervous systemUnaffected littermatesSodium channelsLittermatesPattern of expressionChannel subunitsRatsGreater expressionSitu hybridization techniqueUnaffected animalsPrevious reportsCloning of a bovine renal epithelial Na+ channel subunit
Fuller C, Awayda M, Arrate M, Bradford A, Morris R, Canessa C, Rossier B, Benos D. Cloning of a bovine renal epithelial Na+ channel subunit. American Journal Of Physiology 1995, 269: c641-c654. PMID: 7573394, DOI: 10.1152/ajpcell.1995.269.3.c641.Peer-Reviewed Original ResearchConceptsChannel subunitsOpen reading frameProtein kinase A.Gamma-ENaC subunitsCDNA expression libraryProtein kinase CVitro translationCDNA clonesBovine cDNAXenopus laevis oocytesPancreatic microsomesAcid proteinReading frameNovel isoformBovine homologueExpression libraryConsensus sequenceKinase CBase pairsAlpha-hENaCXenopus oocytesChimeric channelsHuman counterpartLaevis oocytesSubunitsRelative expression of the human epithelial Na+ channel subunits in normal and cystic fibrosis airways
Burch L, Talbot C, Knowles M, Canessa C, Rossier B, Boucher R. Relative expression of the human epithelial Na+ channel subunits in normal and cystic fibrosis airways. American Journal Of Physiology 1995, 269: c511-c518. PMID: 7653534, DOI: 10.1152/ajpcell.1995.269.2.c511.Peer-Reviewed Original ResearchConceptsAirway epitheliumSuperficial epitheliumCF airwaysGamma-ENaC mRNACF airway diseaseENaC subunit mRNAsCystic fibrosis airway epitheliaCF airway epitheliaAirway diseaseSitu hybridization studiesDuctal epitheliumCF transmembrane conductance regulator (CFTR) proteinRibonuclease protection assaysAcinar epitheliumMolecular pathogenesisCystic fibrosisChannel mRNAInhibitory regulationSubunit mRNAsEpitheliumChannel subunitsRatio of alphaAirwayRelative expressionPathogenesis
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