ArticleFrontiers in physiology2013
Characterization of N-terminally mutated cardiac Na(+) channels associated with long QT syndrome 3 and Brugada syndrome.
Article in Frontiers in physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Variability in reported midpoints of (in)activation of cardiac INa.The Journal of general physiology · 2025Pooled it
- Biophysical mechanisms of myocardium sodium channelopathies.Pflugers Archiv : European journal of physiology · 2024Review
- Automated Patch-Clamp and Induced Pluripotent Stem Cell-Derived Cardiomyocytes: A Synergistic Approach in the Study of Brugada Syndrome.International journal of molecular sciences · 2023Review
- Brugada Syndrome: From Molecular Mechanisms and Genetics to Risk Stratification.International journal of molecular sciences · 2023Review
- Coupling the Cardiac Voltage-Gated Sodium Channel to Channelrhodopsin-2 Generates Novel Optical Switches for Action Potential Studies.Membranes · 2022Article
- Relationship between sodium channel function and clinical phenotype in SCN5A variants associated with Brugada syndrome.Human mutation · 2020Article
- Characterization of an N-terminal NaBMC medical genetics · 2020Article
- Action potentials in Xenopus oocytes triggered by blue light.The Journal of general physiology · 2020Article
- SCN5A mutation and a short coupled variant of Torsades de Pointes originating from the right ventricle: A case report.Journal of cardiology cases · 2020Article
- Brugada Syndrome: Oligogenic or Mendelian Disease?International journal of molecular sciences · 2020Review
- Pooled Analysis of Risk Stratification of Spontaneous Type 1 Brugada ECG: Focus on the Influence of Gender and EPS.Frontiers in physiology · 2018Article
- Sudden arrhythmic death: from basic science to clinical practice.Frontiers in physiology · 2013Article
- NovelMolecular painArticle
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3 authors.
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Abstract
Mutations in SCN5A, the gene encoding the cardiac voltage-gated Na(+) channel hNav1.5, can result in life-threatening arrhythmias including long QT syndrome 3 (LQT3) and Brugada syndrome (BrS). Numerous mutant hNav1.5 channels have been characterized upon heterologous expression and patch-clamp recordings during the last decade. These studies revealed functionally important regions in hNav1.5 and provided insight into gain-of-function or loss-of-function channel defects underlying LQT3 or BrS, respectively. The N-terminal region of hNav1.5, however, has not yet been investigated in detail, although several mutations were reported in the literature. In the present study we investigated three mutant channels, previously associated with LQT3 (G9V, R18W, V125L), and six mutant channels, associated with BrS (R18Q, R27H, G35S, V95I, R104Q, K126E). We applied both the two-microelectrode voltage clamp technique, using cRNA-injected Xenopus oocytes, and the whole-cell patch clamp technique using transfected HEK293 cells. Surprisingly, four out of the nine mutations did not affect channel properties. Gain-of-function, as typically observed in LQT3 mutant channels, was observed only in R18W and V125L, whereas loss-of-function, frequently found in BrS mutants, was found only in R27H, R104Q, and K126E. Our results indicate that the hNav1.5 N-terminus plays an important role for channel kinetics and stability. At the same time, we suggest that additional mechanisms, as e.g., disturbed interactions of the Na(+) channel N-terminus with other proteins, contribute to severe clinical phenotypes.
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