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
2017
Kv3 Channels: Enablers of Rapid Firing, Neurotransmitter Release, and Neuronal Endurance
Kaczmarek LK, Zhang Y. Kv3 Channels: Enablers of Rapid Firing, Neurotransmitter Release, and Neuronal Endurance. Physiological Reviews 2017, 97: 1431-1468. PMID: 28904001, PMCID: PMC6151494, DOI: 10.1152/physrev.00002.2017.Peer-Reviewed Original ResearchConceptsKv3 channelsAuditory brain stem neuronsNeurotransmitter releaseBrain stem neuronsOngoing neuronal activityFire action potentialsHigh-frequency firingChannel genesStem neuronsGABAergic interneuronsMultiple protein isoformsCertain neuronsProtein-protein interactionsNeuronal activityNeuronal functionAlzheimer's diseaseNeurological disordersAction potentialsPurkinje cellsUnique expression patternKv3 familyNeuronsAbnormal regulationProtein isoformsProtein kinase
2016
The need for new approaches in CNS drug discovery: Why drugs have failed, and what can be done to improve outcomes
Gribkoff VK, Kaczmarek LK. The need for new approaches in CNS drug discovery: Why drugs have failed, and what can be done to improve outcomes. Neuropharmacology 2016, 120: 11-19. PMID: 26979921, PMCID: PMC5820030, DOI: 10.1016/j.neuropharm.2016.03.021.Peer-Reviewed Original ResearchConceptsCNS drug discoveryClinical failure rateDisease-modifying treatmentsEffects of drugsMajor neurodegenerative disordersMajor neurodegenerative diseasesNon-CNS drugsFuture CNSCNS diseaseFailure rateCNS disordersCNS targetsBasic research findingsField of neuropharmacologyCNS drugsClinical developmentNeuronal functionNeurological disordersNeurodegenerative disordersNeurodegenerative diseasesHigh failure rateDrug discoveryCNSNew drugsDrugs