ArticleCirculation. Cardiovascular genetics2011
A novel strategy using cardiac sodium channel polymorphic fragments to rescue trafficking-deficient SCN5A mutations.
Article in Circulation. Cardiovascular genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Variability in reported midpoints of (in)activation of cardiac INa.The Journal of general physiology · 2025Pooled it
- Genomic and Non-Genomic Regulatory Mechanisms of the Cardiac Sodium Channel in Cardiac Arrhythmias.International journal of molecular sciences · 2022Review
- The Genetics and Epigenetics of Ventricular Arrhythmias in Patients Without Structural Heart Disease.Frontiers in cardiovascular medicine · 2022Review
- Expression defect of the rare variant/Brugada mutation R1512W depends upon the SCN5A splice variant background and can be rescued by mexiletine and the common polymorphism H558R.Channels (Austin, Tex.) · 2021Article
- Novel SCN5A variants identified in a group of Iranian Brugada syndrome patients.Functional & integrative genomics · 2021Article
- Reduced current density, partially rescued by mexiletine, and depolarizing shift in activation of SCN5A W374G channels as a cause of severe form of Brugada syndrome.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2021Article
- Long QT syndrome - Bench to bedside.Heart rhythm O2 · 2021Article
- A Heart Failure-AssociatedFrontiers in physiology · 2021Article
- Life Cycle of the Cardiac Voltage-Gated Sodium Channel NaFrontiers in physiology · 2020Review
- Kir2.1 & NaCirculation research · 2018Article
- Sodium channel current loss of function in induced pluripotent stem cell-derived cardiomyocytes from a Brugada syndrome patient.Journal of molecular and cellular cardiology · 2018Article
- Mexiletine rescues a mixed biophysical phenotype of the cardiac sodium channel arising from the SCN5A mutation, N406K, found in LQT3 patients.Channels (Austin, Tex.) · 2018Article
- Voltage-gated sodium channels assemble and gate as dimers.Nature communications · 2017Article
- H558R, a common SCN5A polymorphism, modifies the clinical phenotype of Brugada syndrome by modulating DNA methylation of SCN5A promoters.Journal of biomedical science · 2017Article
- Article
- Further Insights in the Most Common SCN5A Mutation Causing Overlapping Phenotype of Long QT Syndrome, Brugada Syndrome, and Conduction Defect.Journal of the American Heart Association · 2016Article
- Cardiac Sodium Channel Mutations: Why so Many Phenotypes?Current topics in membranes · 2016Article
- Brugada syndrome risk loci seem protective against atrial fibrillation.European journal of human genetics : EJHG · 2014Article
- Cardiac sodium channel mutations: why so many phenotypes?Nature reviews. Cardiology · 2014Review
- Brugada syndrome disease phenotype explained in apparently benign sodium channel mutations.Circulation. Cardiovascular genetics · 2014Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundBrugada syndrome (BrS) is associated with mutations in the cardiac sodium channel (Na(v)1.5). We previously reported that the function of a trafficking-deficient BrS Na(v)1.5 mutation, R282H, could be restored by coexpression with the sodium channel polymorphism H558R. Here, we tested the hypothesis that peptide fragments from Na(v)1.5, spanning the H558R polymorphism, can be used to restore trafficking of trafficking-deficient BrS sodium channel mutations. METHODS AND
resultsWhole-cell patch clamping revealed that cotransfection in human embryonic kidney (HEK293) cells of the R282H channel with either the 40- or 20-amino acid cDNA fragments of Na(v)1.5 containing the H558R polymorphism restored trafficking of this mutant channel. Fluorescence resonance energy transfer suggested that the trafficking-deficient R282H channel was misfolded, and this was corrected on coexpression with R558-containing peptides that restored trafficking of the R282H channel. Importantly, we also expressed the peptide spanning the H558R polymorphism with 8 additional BrS Na(v)1.5 mutations with reduced currents and demonstrated that the peptide was able to restore significant sodium currents in 4 of them.
conclusionsIn the present study, we demonstrate that small peptides, spanning the H558R polymorphism, are sufficient to restore the trafficking defect of BrS-associated Na(v)1.5 mutations. Our findings suggest that it might be possible to use short cDNA constructs as a novel strategy tailored to specific disease-causing mutants of BrS.
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