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
The NaVy paradox: reducing sodium currents increases excitability
Kaczmarek LK. The NaVy paradox: reducing sodium currents increases excitability. Trends In Neurosciences 2021, 44: 767-768. PMID: 34373125, PMCID: PMC8813127, DOI: 10.1016/j.tins.2021.07.008.Peer-Reviewed Original Research
2019
Loss of NaV1.2-Dependent Backpropagating Action Potentials in Dendrites Contributes to Autism and Intellectual Disability
Kaczmarek LK. Loss of NaV1.2-Dependent Backpropagating Action Potentials in Dendrites Contributes to Autism and Intellectual Disability. Neuron 2019, 103: 551-553. PMID: 31437449, DOI: 10.1016/j.neuron.2019.07.032.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAutistic DisorderDendritesHumansIntellectual DisabilityNAV1.2 Voltage-Gated Sodium ChannelPrefrontal CortexAn Epilepsy-Associated KCNT1 Mutation Enhances Excitability of Human iPSC-Derived Neurons by Increasing Slack KNa Currents
Quraishi IH, Stern S, Mangan KP, Zhang Y, Ali SR, Mercier MR, Marchetto MC, McLachlan MJ, Jones EM, Gage FH, Kaczmarek LK. An Epilepsy-Associated KCNT1 Mutation Enhances Excitability of Human iPSC-Derived Neurons by Increasing Slack KNa Currents. Journal Of Neuroscience 2019, 39: 7438-7449. PMID: 31350261, PMCID: PMC6759030, DOI: 10.1523/jneurosci.1628-18.2019.Peer-Reviewed Original ResearchConceptsSevere epileptic encephalopathyAction potentialsEpileptic encephalopathyFiring rateCurrent-clamp recordingsSodium-activated potassium channelsMaximal firing rateIntensity of firingMean firing rateKCNT1 mutationsCortical neuronsCell-autonomous mechanismsEffective treatmentHuman neuronsPotassium currentActive neuronsNeuronsPotassium channelsCompensatory changesDisease-causing mutationsHyperexcitabilityHuman iPSCEncephalopathyExcitabilityStem cells
2017
Pharmacological modulation of Kv3.1 mitigates auditory midbrain temporal processing deficits following auditory nerve damage
Chambers AR, Pilati N, Balaram P, Large CH, Kaczmarek LK, Polley DB. Pharmacological modulation of Kv3.1 mitigates auditory midbrain temporal processing deficits following auditory nerve damage. Scientific Reports 2017, 7: 17496. PMID: 29235497, PMCID: PMC5727503, DOI: 10.1038/s41598-017-17406-x.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAuditory PathwaysAuditory PerceptionCochlear NerveCompulsive BehaviorDisease Models, AnimalImidazolesMembrane Transport ModulatorsMesencephalonMiceModels, BiologicalNeuronsOuabainPyrimidinesRecovery of FunctionShaw Potassium ChannelsTissue Culture TechniquesVestibulocochlear Nerve DiseasesConceptsTemporal processing deficitsAuditory nerve damageCochlear nerve synapsesTemporal sound featuresCentral auditory pathwayAuditory brainstem neuronsPromising therapeutic approachPatch-clamp recordingsOtotoxic drug exposurePrecise temporal codingTemporal firing patternsHigh-threshold channelsVoltage-gated potassium channelsProcessing deficitsNerve damageBrainstem neuronsAfferent inputCentral neuronsDrug exposureAfferent synapsesContralateral earSystemic injectionCompensatory plasticityTherapeutic approachesAuditory cortex
2016
Physiological modulators of Kv3.1 channels adjust firing patterns of auditory brain stem neurons
Brown MR, El-Hassar L, Zhang Y, Alvaro G, Large CH, Kaczmarek LK. Physiological modulators of Kv3.1 channels adjust firing patterns of auditory brain stem neurons. Journal Of Neurophysiology 2016, 116: 106-121. PMID: 27052580, PMCID: PMC4961756, DOI: 10.1152/jn.00174.2016.Peer-Reviewed Original ResearchConceptsKv3.1 channelsAuditory brain stem neuronsAuditory brain stemBrain stem neuronsBrain slice recordingsKv3.1 potassium channelVoltage of activationMNTB neuronsStem neuronsTrapezoid bodyBrain stemMedial nucleusKv3.1 currentsNeuronal excitabilitySlice recordingsTherapeutic benefitImidazolidinedione derivativesAction potentialsPhysiological modulatorPotassium channelsResting potentialsNeuronsSingle-channel recordingsChinese hamster ovary cellsPharmaceutical modulation
2013
A sodium-activated potassium channel supports high-frequency firing and reduces energetic costs during rapid modulations of action potential amplitude
Markham MR, Kaczmarek LK, Zakon HH. A sodium-activated potassium channel supports high-frequency firing and reduces energetic costs during rapid modulations of action potential amplitude. Journal Of Neurophysiology 2013, 109: 1713-1723. PMID: 23324315, PMCID: PMC3628015, DOI: 10.1152/jn.00875.2012.Peer-Reviewed Original Research
2012
Gradients and Modulation of K+ Channels Optimize Temporal Accuracy in Networks of Auditory Neurons
Kaczmarek LK. Gradients and Modulation of K+ Channels Optimize Temporal Accuracy in Networks of Auditory Neurons. PLOS Computational Biology 2012, 8: e1002424. PMID: 22438799, PMCID: PMC3305353, DOI: 10.1371/journal.pcbi.1002424.Peer-Reviewed Original ResearchConceptsSpontaneous activityPotassium currentRandom spontaneous activityAuditory brainstem neuronsAuditory brainstem nucleiSubset of neuronsMaximal firing rateHigh rateNormal auditory processingPattern of stimulationBrainstem neuronsBrainstem nucleiSynaptic outputAuditory neuronsChannel expressionSuch neuronsStimulus rateAction potentialsTonotopic axisSound stimulationFiring ratePotassium conductanceNeuronsKv3 channelsIndividual neurons
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
Amino‐termini isoforms of the Slack K+ channel, regulated by alternative promoters, differentially modulate rhythmic firing and adaptation
Brown MR, Kronengold J, Gazula V, Spilianakis CG, Flavell RA, Von Hehn CA, Bhattacharjee A, Kaczmarek LK. Amino‐termini isoforms of the Slack K+ channel, regulated by alternative promoters, differentially modulate rhythmic firing and adaptation. The Journal Of Physiology 2008, 586: 5161-5179. PMID: 18787033, PMCID: PMC2652154, DOI: 10.1113/jphysiol.2008.160861.Peer-Reviewed Original ResearchAction PotentialsAdaptation, PhysiologicalAmino Acid SequenceAnimalsBrainCloning, MolecularGene Expression RegulationMiceMice, Inbred C57BLMolecular Sequence DataNerve Tissue ProteinsNeuronsPotassium ChannelsPotassium Channels, Sodium-ActivatedPromoter Regions, GeneticProtein IsoformsRatsRNA, MessengerRepetitive 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
Sodium‐dependent potassium channels of a Slack‐like subtype contribute to the slow afterhyperpolarization in lamprey spinal neurons
Wallén P, Robertson B, Cangiano L, Löw P, Bhattacharjee A, Kaczmarek LK, Grillner S. Sodium‐dependent potassium channels of a Slack‐like subtype contribute to the slow afterhyperpolarization in lamprey spinal neurons. The Journal Of Physiology 2007, 585: 75-90. PMID: 17884929, PMCID: PMC2375474, DOI: 10.1113/jphysiol.2007.138156.Peer-Reviewed Original ResearchConceptsSodium-dependent potassium channelSlow afterhyperpolarizationAction potentialsPotassium channelsSingle action potentialLamprey spinal neuronsLamprey spinal cordLamprey locomotor networkSlow AHPLarge neuronsSpinal neuronsSpinal cordLocomotor networksBurst activityKNa channelsDistinct immunoreactivityGray matterReversal potentialNeuronsChloride injectionAfterhyperpolarizationRapid activationFunctional roleHigh-level activitiesSlack geneSlack and Slick KNa Channels Regulate the Accuracy of Timing of Auditory Neurons
Yang B, Desai R, Kaczmarek LK. Slack and Slick KNa Channels Regulate the Accuracy of Timing of Auditory Neurons. Journal Of Neuroscience 2007, 27: 2617-2627. PMID: 17344399, PMCID: PMC6672517, DOI: 10.1523/jneurosci.5308-06.2007.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAnimals, NewbornAuditory PathwaysBithionolBrain StemComputer SimulationElectric ConductivityElectric StimulationElectrophysiologyIn Vitro TechniquesMiceModels, NeurologicalNerve Tissue ProteinsNeuronsNeurons, AfferentPotassium ChannelsPotassium Channels, Sodium-ActivatedReaction TimeSodium
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 localizationFor K+ channels, Na+ is the new Ca2+
Bhattacharjee A, Kaczmarek LK. For K+ channels, Na+ is the new Ca2+. Trends In Neurosciences 2005, 28: 422-428. PMID: 15979166, DOI: 10.1016/j.tins.2005.06.003.Peer-Reviewed Original ResearchAminoglycosides block the Kv3.1 potassium channel and reduce the ability of inferior colliculus neurons to fire at high frequencies
Liu S, Kaczmarek LK. Aminoglycosides block the Kv3.1 potassium channel and reduce the ability of inferior colliculus neurons to fire at high frequencies. Developmental Neurobiology 2005, 62: 439-452. PMID: 15547932, DOI: 10.1002/neu.20112.Peer-Reviewed Original ResearchConceptsInferior colliculus neuronsKv3.1 potassium channelColliculus neuronsKv3.1 currentsHearing lossAuditory neuronsPotassium channelsInhibition of Kv3.1Progressive hearing lossRate of repolarizationAuditory nucleiPotassium currentFiring propertiesPipette solutionAction potentialsNeuronsHigh frequencyEffect of streptomycinExtracellular TEAKv3.1 geneKv3.1 channelsAminoglycoside antibioticsStreptomycinKv3.1Presence of streptomycin
2003
Functional Specialization of Male and Female Vocal Motoneurons
Yamaguchi A, Kaczmarek LK, Kelley DB. Functional Specialization of Male and Female Vocal Motoneurons. Journal Of Neuroscience 2003, 23: 11568-11576. PMID: 14684859, PMCID: PMC6740944, DOI: 10.1523/jneurosci.23-37-11568.2003.Peer-Reviewed Original ResearchModulation 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
2001
Presynaptic target of Ca2+ action on neuropeptide and acetylcholine release in Aplysia californica
Ohnuma K, Whim M, Fetter R, Kaczmarek L, Zucker R. Presynaptic target of Ca2+ action on neuropeptide and acetylcholine release in Aplysia californica. The Journal Of Physiology 2001, 535: 647-662. PMID: 11559764, PMCID: PMC2278817, DOI: 10.1111/j.1469-7793.2001.00647.x.Peer-Reviewed Original ResearchConceptsSensory neuronsCholinergic synapsesPeptidergic synapsesAcetylcholine releasePostsynaptic responsesAction potentialsMost synaptic contactsIntracellular calcium concentrationPeptidergic vesiclesSingle action potentialAplysia californicaDose-response curveDense-core vesiclesNeuron B2Neuron B3Cholinergic transmissionSynaptic contactsLinear dose-response curvePostsynaptic neuronsPresynaptic neuronsCholinergic releasePresynaptic targetCholinergic vesiclesReleasable poolPatch pipette