ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Multistate structural modeling and voltage-clamp analysis of epilepsy/autism mutation Kv10.2-R327H demonstrate the role of this residue in stabilizing the channel closed state.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Crosstalk of KCNH1 and KCNH5 gain-of-function mutations leading to epilepsy and neurodevelopmental disorders.Molecular brain · 2026Article
- A Novel De Novo Variant in KCNH5 in a Patient with Refractory Epileptic Encephalopathy.Internal medicine (Tokyo, Japan) · 2025Article
- Review
- Clinical phenotypes of developmental and epileptic encephalopathy-related recurrentEpilepsy & behavior reports · 2024Article
- Voltage-gated potassium channels and genetic epilepsy.Frontiers in neurology · 2024Review
- Neurodevelopmental and Epilepsy Phenotypes in Individuals With Missense Variants in the Voltage-Sensing and Pore Domains ofNeurology · 2023Article
- Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum.Physiological reviews · 2023Review
- A novel loss-of-function mutation of the voltage-gated potassium channel Kv10.2 involved in epilepsy and autism.Orphanet journal of rare diseases · 2022Article
- Clinical Feature, Treatment, and KCNH5 Mutations in Epilepsy.Frontiers in pediatrics · 2022Article
- NRXN1αBMC neuroscience · 2021Article
- Deletion of Kv10.2 Causes Abnormal Dendritic Arborization and Epilepsy Susceptibility.Neurochemical research · 2020Article
- Reduced GABAergic Neuron Excitability, Altered Synaptic Connectivity, and Seizures in a KCNT1 Gain-of-Function Mouse Model of Childhood Epilepsy.Cell reports · 2020Article
- Chlorpromazine binding to the PAS domains uncovers the effect of ligand modulation on EAG channel activity.The Journal of biological chemistry · 2020Article
- Increased Expression of Kv10.2 in the Hippocampus Attenuates Valproic Acid-Induced Autism-Like Behaviors in Rats.Neurochemical research · 2019Article
- Myotonia in a patient with a mutation in an S4 arginine residue associated with hypokalaemic periodic paralysis and a concomitant synonymous CLCN1 mutation.Scientific reports · 2019Article
- Voltage-dependent activation in EAG channels follows a ligand-receptor rather than a mechanical-lever mechanism.The Journal of biological chemistry · 2019Article
- Potassium Channel Gain of Function in Epilepsy: An Unresolved Paradox.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2018Article
- Ether-à-go-go KThe Journal of physiology · 2018Review
- Ion Channel Genes and Epilepsy: Functional Alteration, Pathogenic Potential, and Mechanism of Epilepsy.Neuroscience bulletin · 2017Review
- Nav1.7-A1632G Mutation from a Family with Inherited Erythromelalgia: Enhanced Firing of Dorsal Root Ganglia Neurons Evoked by Thermal Stimuli.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
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7 authors.
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Abstract
Voltage-gated potassium channel Kv10.2 (KCNH5) is expressed in the nervous system, but its functions and involvement in human disease are poorly understood. We studied a human Kv10.2 channel mutation (R327H) recently identified in a child with epileptic encephalopathy and autistic features. Using multistate structural modeling, we demonstrate that the Arg327 residue in the S4 helix of voltage-sensing domain has strong ionic interactions with negatively charged residues within the S1-S3 helices in the resting (closed) and early-activation state but not in the late-activation and fully-activated (open) state. The R327H mutation weakens ionic interactions between residue 327 and these negatively charged residues, thus favoring channel opening. Voltage-clamp analysis showed a strong hyperpolarizing (∼70 mV) shift of voltage dependence of activation and an acceleration of activation. Our results demonstrate the critical role of the Arg327 residue in stabilizing the channel closed state and explicate for the first time the structural and functional change of a Kv10.2 channel mutation associated with neurological disease.
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