ArticleDisease models & mechanisms
Episodic ataxia type 1 mutations differentially affect neuronal excitability and transmitter release.
Article in Disease models & mechanisms. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- A conifer metabolite corrects episodic ataxia type 1 by voltage sensor-mediated ligand activation of Kv1.1.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Anti-seizure gene therapy for focal cortical dysplasia.Brain : a journal of neurology · 2024Article
- AAV-based in vivo gene therapy for neurological disorders.Nature reviews. Drug discovery · 2023Review
- Native American ataxia medicines rescue ataxia-linked mutant potassium channel activity via binding to the voltage sensing domain.Nature communications · 2023Article
- On-demand cell-autonomous gene therapy for brain circuit disorders.Science (New York, N.Y.) · 2022Article
- Case report: A novel loss-of-function pathogenic variant in the KCNA1 cytoplasmic N-terminus causing carbamazepine-responsive type 1 episodic ataxia.Frontiers in neurology · 2022Article
- Kv1.1 channels regulate early postnatal neurogenesis in mouse hippocampus via the TrkB signaling pathway.eLife · 2021Article
- New Trends and Most Promising Therapeutic Strategies for Epilepsy Treatment.Frontiers in neurology · 2021Review
- Kv1.1 Channelopathies: Pathophysiological Mechanisms and Therapeutic Approaches.International journal of molecular sciences · 2020Review
- Clinical Spectrum ofInternational journal of molecular sciences · 2020Review
- In vivo CRISPRa decreases seizures and rescues cognitive deficits in a rodent model of epilepsy.Brain : a journal of neurology · 2020Article
- Autaptic Cultures: Methods and Applications.Frontiers in synaptic neuroscience · 2020Article
- Epilepsy Therapy Goes Viral.Epilepsy currents · 2019Article
- Epilepsy Gene Therapy Using an Engineered Potassium Channel.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Discovery of a small molecule modulator of the Kv1.1/Kvβ1 channel complex that reduces neuronal excitability and in vitro epileptiform activity.CNS neuroscience & therapeutics · 2019Article
- Ion Channels in Genetic Epilepsy: From Genes and Mechanisms to Disease-Targeted Therapies.Pharmacological reviews · 2018Review
- Heparan Sulfates Support Pyramidal Cell Excitability, Synaptic Plasticity, and Context Discrimination.Cerebral cortex (New York, N.Y. : 1991) · 2017Article
- Clinical heterogeneity associated with KCNA1 mutations include cataplexy and nonataxic presentations.Neurogenetics · 2016Article
- Auditory deficits of Kcna1 deletion are similar to those of a monaural hearing impairment.Hearing research · 2015Article
- Voltage-gated potassium channels at the crossroads of neuronal function, ischemic tolerance, and neurodegeneration.Translational stroke research · 2014Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Heterozygous mutations of KCNA1, the gene encoding potassium channel Kv1.1 subunits, cause episodic ataxia type 1 (EA1), which is characterized by paroxysmal cerebellar incoordination and interictal myokymia. Some mutations are also associated with epilepsy. Although Kv1.1-containing potassium channels play important roles in neuronal excitability and neurotransmitter release, it is not known how mutations associated with different clinical features affect the input-output relationships of individual neurons. We transduced rat hippocampal neurons, which were cultured on glial micro-islands, with lentiviruses expressing wild-type or mutant human KCNA1, and injected either depolarizing currents to evoke action potentials or depolarizing voltage commands to evoke autaptic currents. alpha-Dendrotoxin and tetraethylammonium allowed a pharmacological dissection of potassium currents underlying excitability and neurotransmission. Overexpression of wild-type Kv1.1 decreased both neuronal excitability and neurotransmitter release. By contrast, the C-terminus-truncated R417stop mutant, which is associated with severe drug-resistant EA1, had the opposite effect: increased excitability and release probability. Another mutant, T226R, which is associated with EA1 that is complicated by contractures and epilepsy, had no detectable effect on neuronal excitability; however, in common with R417stop, it markedly enhanced neurotransmitter release. The results provide direct evidence that EA1 mutations increase neurotransmitter release, and provide an insight into mechanisms underlying the phenotypic differences that are associated with different mutations.
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