ArticleThe Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry2018
Potassium Channel Gain of Function in Epilepsy: An Unresolved Paradox.
Article in The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 2 of them syntheses that pooled it.
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Who cites it
87 citing papers in PubMed, 2 syntheses or guidelines pooled it, 150 citations in OpenAlex.
- Efficacy of anti-seizure medications and alternative therapies (ketogenic diet, CBD, and quinidine) in KCNT1-related epilepsy: A systematic review.Epilepsia open · 2024Pooled it
- Intellectual Disability and Potassium Channelopathies: A Systematic Review.Frontiers in genetics · 2020Pooled it
- Development of an integrated predictive model for postoperative glioma-related epilepsy using gene-signature and clinical data.BMC cancer · 2023Trial
- Expanding the Phenotypic and Functional Evidence for KCNK3 as a Neurodevelopmental Disorder Gene: A New Chinese Case and Drosophila Validation.Clinical genetics · 2026Article
- Equivalent gain-of-function variants in KCNK3 and KCNK9 and their contribution to distinct TASK K2P channelopathies.The Journal of general physiology · 2026Article
- An epilepsy-associated KV3.1 potassium channel variant acts via dominant-positive effect.The Journal of general physiology · 2026Article
- Fever-like temperatures improve cognitive deficits in the Scn2a autism mouse model via increases in potassium channel activity.Molecular psychiatry · 2026Article
- Unraveling the mechanisms of slack channel mutations in epileptic disorders.Acta epileptologica · 2026Review
- The molecular basis of KCNH1-related epileptic encephalopathy and the challenge of developing targeted therapeutics.Brain : a journal of neurology · 2026Review
- Expanding the phenotypic and genotypic spectrum ofBrain communications · 2026Article
- Quantum Mechanical Mechanisms in the Therapeutic Effects of Spinal Cord Stimulation to Treat Chronic Neuropathic Pain: A Quantum Computational Model.Journal of pain research · 2026Article
- Human iPSC-derived glutamatergic neurons with pathogenic KCNQ2 variants display hyperactive bursting phenotypes.Neurobiology of disease · 2025Article
- Tcf4 Deficiency causes recurrent seizures in mice.Progress in neurobiology · 2025Article
- kcnb1 loss of function in zebrafish causes neurodevelopmental and epileptic disorders associated with γ-aminobutyric acid dysregulation.Epilepsia · 2025Article
- H- and m-channel overexpression promotes seizure-like events by impairing the ability of inhibitory neurons to process correlated inputs.PLoS computational biology · 2025Article
- Targeting Kv7 Potassium Channels for Epilepsy.CNS drugs · 2025Review
- Association of Voltage-Gated Potassium Channel Polymorphisms with the Risk and Prognosis of Epilepsy in the Saudi Population: A Case-Control Study.Medicina (Kaunas, Lithuania) · 2025Article
- Constitutive opening of the Kv7.2 pore activation gate causesProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Voltage-Gated Ion Channel Compensatory Effect in DEE: Implications for Future Therapies.Cells · 2024Review
- The complex molecular epileptogenesis landscape of glioblastoma.Cell reports. Medicine · 2024Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Exome and targeted sequencing have revolutionized clinical diagnosis. This has been particularly striking in epilepsy and neurodevelopmental disorders, for which new genes or new variants of preexisting candidate genes are being continuously identified at increasing rates every year. A surprising finding of these efforts is the recognition that gain of function potassium channel variants are actually associated with certain types of epilepsy, such as malignant migrating partial seizures of infancy or early-onset epileptic encephalopathy. This development has been difficult to understand as traditionally potassium channel loss-of-function, not gain-of-function, has been associated with hyperexcitability disorders. In this article, we describe the current state of the field regarding the gain-of-function potassium channel variants associated with epilepsy (KCNA2, KCNB1, KCND2, KCNH1, KCNH5, KCNJ10, KCNMA1, KCNQ2, KCNQ3, and KCNT1) and speculate on the possible cellular mechanisms behind the development of seizures and epilepsy in these patients. Understanding how potassium channel gain-of-function leads to epilepsy will provide new insights into the inner working of neural circuits and aid in developing new therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.