2016
Stimulation 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 disabilityActivatorKv3.3 Channels Bind Hax-1 and Arp2/3 to Assemble a Stable Local Actin Network that Regulates Channel Gating
Zhang Y, Zhang XF, Fleming MR, Amiri A, El-Hassar L, Surguchev AA, Hyland C, Jenkins DP, Desai R, Brown MR, Gazula VR, Waters MF, Large CH, Horvath TL, Navaratnam D, Vaccarino FM, Forscher P, Kaczmarek LK. Kv3.3 Channels Bind Hax-1 and Arp2/3 to Assemble a Stable Local Actin Network that Regulates Channel Gating. Cell 2016, 165: 434-448. PMID: 26997484, PMCID: PMC4826296, DOI: 10.1016/j.cell.2016.02.009.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonActin-Related Protein 2Actin-Related Protein 2-3 ComplexActin-Related Protein 3Adaptor Proteins, Signal TransducingAmino Acid SequenceCell MembraneMolecular Sequence DataMutationNeuronsPluripotent Stem CellsRac GTP-Binding ProteinsShaw Potassium ChannelsSignal TransductionSpinocerebellar AtaxiasConceptsCytoplasmic C-terminusProline-rich domainPlasma membraneHAX-1Actin nucleationC-terminusCortical actin filament networkLocal actin networkStem cell-derived neuronsActin filament networkCell-derived neuronsAnti-apoptotic proteinsActin cytoskeletonKv3.3 potassium channelActin assemblyActin structuresActin networkArp2/3Channel gatingFilament networkGrowth conesCerebellar neurodegenerationKv3.3TerminusPotassium channels
2015
Membrane Ion Channels and Ion Currents
Levitan I, Kaczmarek L. Membrane Ion Channels and Ion Currents. 2015, 63-84. DOI: 10.1093/med/9780199773893.003.0004.ChaptersSingle ion channelsIon currentMovement of ionsIon channelsParticular ionPlasma membraneSpecialized membrane proteinsMembrane ion channelsIonsAction potential firingNeuronal plasma membranePatch-clamp techniqueMembrane proteinsNeurons resultsCurrentClamp techniqueAction potentialsDetailed characterizationElectrical activityMembrane currentsMembrane voltageChannelsMacroscopic membrane currentsEssential propertiesComplex patternsHow Neurons Communicate: Gap Junctions and Neurosecretion
Levitan I, Kaczmarek L. How Neurons Communicate: Gap Junctions and Neurosecretion. 2015, 153-186. DOI: 10.1093/med/9780199773893.003.0008.ChaptersSynaptic vesiclesSNARE complex proteinsExistence of proteinsSecretion of neurotransmittersComplex proteinsPlasma membraneCytoplasmic vesiclesProteinVesiclesAdjacent cellsGap junctionsSmall moleculesCalcium entryExternal mediumElectrical couplingMembraneNeurosecretionCellsComplex processEndocytosisExocytosisFluorescent dyeMoleculesConnexinsCytoplasmReceptors and Transduction Mechanisms I: Receptors Coupled Directly to Ion Channels
Levitan I, Kaczmarek L. Receptors and Transduction Mechanisms I: Receptors Coupled Directly to Ion Channels. 2015, 239-262. DOI: 10.1093/med/9780199773893.003.0011.ChaptersSensory Receptors
Levitan I, Kaczmarek L. Sensory Receptors. 2015, 295-326. DOI: 10.1093/med/9780199773893.003.0013.Chapters
2014
Use of label-free optical biosensors to detect modulation of potassium channels by G-protein coupled receptors.
Fleming MR, Shamah SM, Kaczmarek LK. Use of label-free optical biosensors to detect modulation of potassium channels by G-protein coupled receptors. Journal Of Visualized Experiments 2014, e51307. PMID: 24562095, PMCID: PMC4122194, DOI: 10.3791/51307.Peer-Reviewed Original ResearchConceptsG protein-coupled receptorsOptical biosensorPlasma membraneLabel-free optical biosensorProtein-protein interactionsIon channelsChannel-protein interactionsExcitable cell typesReceptor tyrosine kinasesProtein-coupled receptorsLigand-induced changesCell surface receptorsPotassium channelsRegulatory proteinsTyrosine kinaseG proteinsProtein behaviorSodium-activated potassium channelsExogenous labelsPhysiological relevanceCell adhesionLiving cellsCell typesHeteromeric channelsSurface receptors
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
2009
Use of optical biosensors to detect modulation of Slack potassium channels by G protein-coupled receptors
Fleming MR, Kaczmarek LK. Use of optical biosensors to detect modulation of Slack potassium channels by G protein-coupled receptors. Journal Of Receptors And Signal Transduction 2009, 29: 173-181. PMID: 19640220, PMCID: PMC3727623, DOI: 10.1080/10799890903056883.Peer-Reviewed Original ResearchConceptsG protein-coupled receptorsProtein-coupled receptorsPlasma membraneIon channelsActivation of GPCRsProtein-protein interactionsDistribution of massExcitable cell typesPotassium channelsRefractive indexHeteromeric channel complexesOptical sensorsOptical biosensorSlack potassium channelsSurface of cellsRegulatory proteinsMass distributionGPCR activationSodium-activated potassium channelsLiving cellsCell typesElectrical propertiesChannel complexBiophysical propertiesProteinThe N-Terminal Domain of Slack Determines the Formation and Trafficking of Slick/Slack Heteromeric Sodium-Activated Potassium Channels
Chen H, Kronengold J, Yan Y, Gazula VR, Brown MR, Ma L, Ferreira G, Yang Y, Bhattacharjee A, Sigworth FJ, Salkoff L, Kaczmarek LK. The N-Terminal Domain of Slack Determines the Formation and Trafficking of Slick/Slack Heteromeric Sodium-Activated Potassium Channels. Journal Of Neuroscience 2009, 29: 5654-5665. PMID: 19403831, PMCID: PMC3688047, DOI: 10.1523/jneurosci.5978-08.2009.Peer-Reviewed Original ResearchConceptsTerminal domainN-terminal domainAlternative splice variantsPotassium channelsSubcellular localizationPlasma membraneMolecular explanationHeteromer formationSplice variantsHeteromeric channelsDistinct rolesSingle-channel levelSubunitsUnitary conductanceCentral neuronsSlack channelsImmunocytochemical studyFiring patternsDomainLocalizationNeuronsGenesTraffickingChannel levelHomomers
2008
PKC-Induced Intracellular Trafficking of CaV2 Precedes Its Rapid Recruitment to the Plasma Membrane
Zhang Y, Helm JS, Senatore A, Spafford JD, Kaczmarek LK, Jonas EA. PKC-Induced Intracellular Trafficking of CaV2 Precedes Its Rapid Recruitment to the Plasma Membrane. Journal Of Neuroscience 2008, 28: 2601-2612. PMID: 18322103, PMCID: PMC2830008, DOI: 10.1523/jneurosci.4314-07.Peer-Reviewed Original ResearchConceptsProtein kinase CActivation of PKCPlasma membraneGrowth conesLatrunculin BIntracellular traffickingActin polymerizationIntact microtubulesIntact actinKinase CChannel insertionPKC activationIon channelsMicrotubule polymerizationRapid recruitmentOrganellesLamellipodiumSubunitsMicrotubulesActinMembraneActivationRecruitmentCone terminalsNew sitesRepetitive 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
Comparative effects of sodium pyrithione evoked intracellular calcium elevation in rodent and primate ventral horn motor neurons
Knox RJ, Keen KL, Luchansky L, Terasawa E, Freyer H, Barbee SJ, Kaczmarek LK. Comparative effects of sodium pyrithione evoked intracellular calcium elevation in rodent and primate ventral horn motor neurons. Biochemical And Biophysical Research Communications 2007, 366: 48-53. PMID: 18053804, DOI: 10.1016/j.bbrc.2007.11.083.Peer-Reviewed Original ResearchConceptsNeuron-specific enolaseMotor neuronsDose-response curveFura-PE3/AMVentral horn motor neuronsAplysia neuronsSpinal cord slicesIntracellular calcium elevationStore-operated calcium entryCord slicesHindlimb weaknessSpecific enolaseSKF-96365Oral administrationRhesus monkey embryosCalcium entryEffects of NAPCalcium elevationPersistent influxNeuronsMammalian neuronsIslet-1Sodium pyrithioneComparative effectsPlasma membrane
2004
Activation 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 analoguesSpeciesThe voltage-gated potassium channel Kv1.3 regulates peripheral insulin sensitivity
Xu J, Wang P, Li Y, Li G, Kaczmarek LK, Wu Y, Koni PA, Flavell RA, Desir GV. The voltage-gated potassium channel Kv1.3 regulates peripheral insulin sensitivity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 3112-3117. PMID: 14981264, PMCID: PMC365752, DOI: 10.1073/pnas.0308450100.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsBiological TransportFastingGlucoseInsulinInterleukin-6JNK Mitogen-Activated Protein KinasesKineticsKv1.3 Potassium ChannelMaleMiceMice, Inbred C57BLMice, KnockoutMice, ObeseMitogen-Activated Protein KinasesModels, BiologicalMuscle, SkeletalPotassium ChannelsPotassium Channels, Voltage-GatedTumor Necrosis Factor-alphaConceptsKv1.3-/- micePeripheral glucose homeostasisPeripheral insulin sensitivityPlasma membraneGene inactivationInsulin sensitivityAmount of GLUT4Skeletal muscleTerminal kinase (JNK) activityGlucose homeostasisAdipose tissueLower blood insulin levelsVoltage-gated potassium channelsInsulin-stimulated glucose uptakeVoltage-gated potassium channel Kv1.3Tumor necrosis factor productionExperimental autoimmune encephalitisBlood insulin levelsHigh-fat dietPotassium channel Kv1.3Tumor necrosis factor secretionPeripheral T lymphocytesKinase activityNecrosis factor productionNumber of tissuesIon channels on intracellular organelles
Kaczmarek L, Jonas E. Ion channels on intracellular organelles. Advances In Molecular And Cell Biology 2004, 32: 433-458. DOI: 10.1016/s1569-2558(03)32018-1.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsExternal signalsIon channelsCellular functionsInner membraneMitochondrial channelsIntracellular membranesPlasma membraneIntracellular organellesMolecular identityCell deathCytoplasmic calcium levelsHandling of calciumRyanodine receptorProperties of channelsCytoplasmic calciumIntracellular storesPotential roleRelease of calciumInternal storesMembraneRegulationKey roleSynaptic transmissionCalcium influxIntracellular calcium
2001
Membrane Ion Channels and Ion Currents
B.Levitan I, Kaczmarek L. Membrane Ion Channels and Ion Currents. 2001, 67-88. DOI: 10.1093/oso/9780195145236.003.0004.Peer-Reviewed Original ResearchPlasma membraneTransmembrane ion flowIon flowMembrane ion channelsMovement of chargeExcellent electrical insulatorTransmembrane ionIon currentIon channelsLipid bilayersMembrane potentialHydrophobic interiorEndogenous electrical activityIonsElectrical insulatorSmall inorganic ionsMembraneTemporal patternsBilayersCellsExternal stimuliInsulatorNerve cellsSpeciesEnergyHow Neurons Communicate: Gap Junctions and Neurosecretion
B.Levitan I, Kaczmarek L. How Neurons Communicate: Gap Junctions and Neurosecretion. 2001, 165-194. DOI: 10.1093/oso/9780195145236.003.0008.Peer-Reviewed Original ResearchCalmodulin Regulates Assembly and Trafficking of SK4/IK1 Ca2+-activated K+ Channels*
Joiner W, Khanna R, Schlichter L, Kaczmarek L. Calmodulin Regulates Assembly and Trafficking of SK4/IK1 Ca2+-activated K+ Channels*. Journal Of Biological Chemistry 2001, 276: 37980-37985. PMID: 11495911, DOI: 10.1074/jbc.m104965200.Peer-Reviewed Original ResearchConceptsChannel assemblyC-terminusAssembly of channelsIon channelsC-terminal domainDistal C-terminal domainCo-immunoprecipitation experimentsCaM-binding domainSurface expressionDominant negative effectProximal C-terminusWhole-cell currentsCellular functionsCaM genesPlasma membraneCaM proteinFree CaMNovel mechanismTraffickingProteinTerminusAssemblyExpressionSK4Domain
1998
Protein Kinase C Regulates a Vesicular Class of Calcium Channels in the Bag Cell Neurons of Aplysia
White B, Nick T, Carew T, Kaczmarek L. Protein Kinase C Regulates a Vesicular Class of Calcium Channels in the Bag Cell Neurons of Aplysia. Journal Of Neurophysiology 1998, 80: 2514-2520. PMID: 9819259, DOI: 10.1152/jn.1998.80.5.2514.Peer-Reviewed Original Research