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
2021
A KCNC1 mutation in epilepsy of infancy with focal migrating seizures produces functional channels that fail to be regulated by PKC phosphorylation
Zhang Y, Ali SR, Nabbout R, Barcia G, Kaczmarek LK. A KCNC1 mutation in epilepsy of infancy with focal migrating seizures produces functional channels that fail to be regulated by PKC phosphorylation. Journal Of Neurophysiology 2021, 126: 532-539. PMID: 34232791, PMCID: PMC8409950, DOI: 10.1152/jn.00257.2021.Peer-Reviewed Original ResearchConceptsFunctional channelsProtein kinase C.Serious human diseasesPotassium channelsWild-type channelsEpilepsy of infancyChannel modulationTerminal domainIon channel mutationsPKC phosphorylationC-terminusNormal neuronal functionChannel proteinsKv3.1 potassium channelRegulatory sitesKinase C.Human diseasesChannel functionPhosphorylationIon channelsMutationsNovo variantsChannel mutationsBiophysical propertiesNeuronal functionPresynaptic Kv3 channels are required for fast and slow endocytosis of synaptic vesicles
Wu XS, Subramanian S, Zhang Y, Shi B, Xia J, Li T, Guo X, El-Hassar L, Szigeti-Buck K, Henao-Mejia J, Flavell RA, Horvath TL, Jonas EA, Kaczmarek LK, Wu LG. Presynaptic Kv3 channels are required for fast and slow endocytosis of synaptic vesicles. Neuron 2021, 109: 938-946.e5. PMID: 33508244, PMCID: PMC7979485, DOI: 10.1016/j.neuron.2021.01.006.Peer-Reviewed Original ResearchConceptsSlow endocytosisVesicle mobilizationF-actin cytoskeletonChannel mutationsPotassium channelsKv3.3 proteinsInhibits endocytosisRapid endocytosisNovel functionF-actinEndocytosisCrucial functionSynaptic vesiclesFamily channelsSynaptic transmissionDiscovery decadesMembrane potentialNeurotransmitter releaseDiverse neurological disordersIon conductanceMutationsReleasable poolMouse nerve terminalsPotassium channel mutationsPathological effects
2012
De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy
Barcia G, Fleming MR, Deligniere A, Gazula VR, Brown MR, Langouet M, Chen H, Kronengold J, Abhyankar A, Cilio R, Nitschke P, Kaminska A, Boddaert N, Casanova JL, Desguerre I, Munnich A, Dulac O, Kaczmarek LK, Colleaux L, Nabbout R. De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy. Nature Genetics 2012, 44: 1255-1259. PMID: 23086397, PMCID: PMC3687547, DOI: 10.1038/ng.2441.Peer-Reviewed Original Research
2006
Functional analysis of a novel potassium channel (KCNA1) mutation in hereditary myokymia
Chen H, von Hehn C, Kaczmarek LK, Ment LR, Pober BR, Hisama FM. Functional analysis of a novel potassium channel (KCNA1) mutation in hereditary myokymia. Neurogenetics 2006, 8: 131-135. PMID: 17136396, PMCID: PMC1820748, DOI: 10.1007/s10048-006-0071-z.Peer-Reviewed Original ResearchConceptsEpisodic ataxiaAdditional clinical featuresAbsence of epilepsyPotassium channel mutationsVoltage-gated potassium channelsPotassium channel gene KCNA1Febrile illnessCerebral palsyClinical featuresExtensor plantarsNonconservative missense mutationElectrophysiological studiesVermiform movementsKv1.1 subunitsLoss of functionMotor delayMyokymiaAutosomal dominant traitPotassium channelsChannel mutationsNovel c.AtaxiaMutation analysisMissense mutationsMutant cRNA