ArticlePloS one2013
Novel HCN2 mutation contributes to febrile seizures by shifting the channel's kinetics in a temperature-dependent manner.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- The Contribution of HCN Channelopathies in Different Epileptic Syndromes, Mechanisms, Modulators, and Potential Treatment Targets: A Systematic Review.Frontiers in molecular neuroscience · 2022Pooled it
- HCAR1-mediated lactate signaling modulates motor behavior and regulates spontaneous firing in Purkinje cells.iScience · 2026Article
- Mechanism of lipid-dependent cold sensitivity in a model ion channel.Nature communications · 2026Article
- HCN2-Associated Neurodevelopmental Disorders: Data from Patients and Xenopus Cell Models.Annals of neurology · 2025Article
- Rescuing DNMT1 fails to fully reverse the molecular and functional repercussions of its loss in mouse embryonic stem cells.Nucleic acids research · 2025Article
- The role of fever in febrile seizures: major implications for fever perception.Frontiers in pediatrics · 2023Article
- Febrile Seizures in Children: A Review.Cureus · 2022Review
- Direct Regulation of Hyperpolarization-Activated Cyclic-Nucleotide Gated (HCN1) Channels by Cannabinoids.Frontiers in molecular neuroscience · 2022Article
- Mutants of the Zebrafish KInternational journal of molecular sciences · 2021Article
- Seizure-related deaths in children: The expanding spectrum.Epilepsia · 2021Article
- A Review of Febrile Seizures: Recent Advances in Understanding of Febrile Seizure Pathophysiology and Commonly Implicated Viral Triggers.Frontiers in pediatrics · 2021Review
- Cardiac and neuronal HCN channelopathies.Pflugers Archiv : European journal of physiology · 2020Review
- The HCN domain is required for HCN channel cell-surface expression and couples voltage- and cAMP-dependent gating mechanisms.The Journal of biological chemistry · 2020Article
- Photodynamic Modification of Native HCN Channels Expressed in Thalamocortical Neurons.ACS chemical neuroscience · 2020Article
- Temperature effects on synaptic transmission and neuronal function in the visual thalamus.PloS one · 2020Article
- Disease-linked mutations alter the stoichiometries of HCN-KCNE2 complexes.Scientific reports · 2019Article
- Characterization of drug binding within the HCN1 channel pore.Scientific reports · 2019Article
- Suppression of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Function in Thalamocortical Neurons Prevents Genetically Determined and Pharmacologically Induced Absence Seizures.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Ion Channels in Genetic Epilepsy: From Genes and Mechanisms to Disease-Targeted Therapies.Pharmacological reviews · 2018Review
- A Loss-of-FunctionFrontiers in molecular neuroscience · 2018Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
Abstract
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated currents, known as I h, are involved in the control of rhythmic activity in neuronal circuits and in determining neuronal properties including the resting membrane potential. Recent studies have shown that HCN channels play a role in seizure susceptibility and in absence and limbic epilepsy including temporal lobe epilepsy following long febrile seizures (FS). This study focused on the potential contributions of abnormalities in the HCN2 isoform and their role in FS. A novel heterozygous missense mutation in HCN2 exon 1 leading to p.S126L was identified in two unrelated patients with FS. The mutation was inherited from the mother who had suffered from FS in a pedigree. To determine the effect of this substitution we conducted whole-cell patch clamp electrophysiology. We found that mutant channels had elevated sensitivity to temperature. More specifically, they displayed faster kinetics at higher temperature. Kinetic shift by change of temperature sensitivity rather than the shift of voltage dependence led to increased availability of I h in conditions promoting FS. Responses to cyclic AMP did not differ between wildtype and mutant channels. Thus, mutant HCN2 channels cause significant cAMP-independent enhanced availability of I h during high temperatures, which may contribute to hyperthermia-induced neuronal hyperexcitability in some individuals with FS.
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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.