ArticlePflugers Archiv : European journal of physiology2016
Mutation in S6 domain of HCN4 channel in patient with suspected Brugada syndrome modifies channel function.
Article in Pflugers Archiv : European journal of physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Phenotypic Effects of a Novel HCN4 c.1494C>A (p.Ser498Arg) Sequence Variation.JACC. Case reports · 2026Article
- Genetic Basis of Brugada Syndrome.Biomedicines · 2025Review
- A Novel Bradycardia-Associated Variant inBiomedicines · 2025Article
- The Role of Human-Induced Pluripotent Stem Cells in Studying Cardiac Channelopathies.International journal of molecular sciences · 2024Review
- Review
- Pacemaker Channels and the Chronotropic Response in Health and Disease.Circulation research · 2024Review
- Age-dependent contribution of intrinsic mechanisms to sinoatrial node function in humans.Scientific reports · 2023Article
- Brugada Syndrome: More than a Monogenic Channelopathy.Biomedicines · 2023Review
- CACNA1C-Related Channelopathies.Handbook of experimental pharmacology · 2023Review
- CaV1.2 channelopathic mutations evoke diverse pathophysiological mechanisms.The Journal of general physiology · 2022Article
- The Genetics and Epigenetics of Ventricular Arrhythmias in Patients Without Structural Heart Disease.Frontiers in cardiovascular medicine · 2022Review
- Review: HCN Channels in the Heart.Current cardiology reviews · 2022Review
- Molecular Remodeling of Cardiac Sinus Node Associated with Acute Chagas Disease Myocarditis.Microorganisms · 2021Article
- Contribution of HCN1 variant to sinus bradycardia: A case report.Journal of arrhythmia · 2021Article
- Towards Mutation-Specific Precision Medicine in Atypical Clinical Phenotypes of Inherited Arrhythmia Syndromes.International journal of molecular sciences · 2021Review
- The mutation L69P in the PAS domain of the hERG potassium channel results in LQTS by trafficking deficiency.Channels (Austin, Tex.) · 2020Article
- Cardiac and neuronal HCN channelopathies.Pflugers Archiv : European journal of physiology · 2020Review
- Article
- Brugada Syndrome: Oligogenic or Mendelian Disease?International journal of molecular sciences · 2020Review
- Mechanical transduction of cytoplasmic-to-transmembrane-domain movements in a hyperpolarization-activated cyclic nucleotide-gated cation channel.The Journal of biological chemistry · 2018Article
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9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diseases such as the sick sinus and the Brugada syndrome are cardiac abnormalities, which can be caused by a number of genetic aberrances. Among them are mutations in HCN4, a gene, which encodes the hyperpolarization-activated, cyclic nucleotide-gated ion channel 4; this pacemaker channel is responsible for the spontaneous activity of the sinoatrial node. The present genetic screening of patients with suspected or diagnosed Brugada or sick sinus syndrome identified in 1 out of 62 samples the novel mutation V492F. It is located in a highly conserved site of hyperpolarization-activated cyclic nucleotide-gated (HCN)4 channel downstream of the filter at the start of the last transmembrane domain S6. Functional expression of mutant channels in HEK293 cells uncovered a profoundly reduced channel function but no appreciable impact on channel synthesis and trafficking compared to the wild type. The inward rectifying HCN4 current could be partially rescued by an expression of heteromeric channels comprising wt and mutant monomers. These heteromeric channels were responsive to cAMP but they required a more negative voltage for activation and they exhibited a lower current density than the wt channel. This suggests a dominant negative effect of the mutation in patients, which carry this heterozygous mutation. Such a modulation of HCN4 activity could be the cause of the diagnosed cardiac abnormality.
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