Featured Publications
An 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
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. 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
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