ArticleCirculation. Cardiovascular genetics2014
A mutation causing Brugada syndrome identifies a mechanism for altered autonomic and oxidant regulation of cardiac sodium currents.
Article in Circulation. Cardiovascular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Variability in reported midpoints of (in)activation of cardiac INa.The Journal of general physiology · 2025Pooled it
- Investigating the role of the I-II linker in Nav1.5 channel function.The Journal of general physiology · 2025Article
- Biophysical mechanisms of myocardium sodium channelopathies.Pflugers Archiv : European journal of physiology · 2024Review
- The dispensability of 14-3-3 proteins for the regulation of human cardiac sodium channel Nav1.5.PloS one · 2024Article
- Novel insights in the pathomechanism of Brugada syndrome and fever-related type 1 ECG changes in a preclinical study using human-induced pluripotent stem cell-derived cardiomyocytes.Clinical and translational medicine · 2023Article
- Electrocardiographic variables associated with underlying Brugada syndrome or drug-induced Type 1 Brugada pattern in patients with slow/fast atrioventricular nodal reentrant tachycardia.Journal of arrhythmia · 2022Article
- Genomic and Non-Genomic Regulatory Mechanisms of the Cardiac Sodium Channel in Cardiac Arrhythmias.International journal of molecular sciences · 2022Review
- Evaluating the Use of Genetics in Brugada Syndrome Risk Stratification.Frontiers in cardiovascular medicine · 2021Article
- High-Throughput Reclassification of SCN5A Variants.American journal of human genetics · 2020Article
- Modulation of the cardiac sodium channel NaJournal of molecular and cellular cardiology · 2020Article
- "Heart Oddity": Intrinsically Reduced Excitability in the Right Ventricle Requires Compensation by Regionally Specific Stress Kinase Function.Frontiers in physiology · 2020Review
- Conduction in the right and left ventricle is differentially regulated by protein kinases and phosphatases: implications for arrhythmogenesis.American journal of physiology. Heart and circulatory physiology · 2019Article
- Phosphorylation of cardiac voltage-gated sodium channel: Potential players with multiple dimensions.Acta physiologica (Oxford, England) · 2019Review
- Dysfunctional Nav1.5 channels due to SCN5A mutations.Experimental biology and medicine (Maywood, N.J.) · 2018Review
- Cardiac Na Channels: Structure to Function.Current topics in membranes · 2016Article
- SCN5A variant that blocks fibroblast growth factor homologous factor regulation causes human arrhythmia.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Physiological and Pathophysiological Insights of Nav1.4 and Nav1.5 Comparison.Frontiers in pharmacology · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe mechanisms of the electrocardiographic changes and arrhythmias in Brugada syndrome (BrS) remain controversial. Mutations in the sodium channel gene, SCN5A, and regulatory proteins that reduce or eliminate sodium current (INa) have been linked to BrS. We studied the properties of a BrS-associated SCN5A mutation in a protein kinase A (PKA) consensus phosphorylation site, R526H. METHODS AND
resultsIn vitro PKA phosphorylation was detected in the I-II linker peptide of wild-type (WT) channels but not R526H or S528A (phosphorylation site) mutants. Cell surface expression of R526H and S528A channels was reduced compared with WT. Whole-cell INa through all channel variants revealed no significant differences in the steady-state activation, inactivation, and recovery from inactivation. Peak current densities of the mutants were significantly reduced compared with WT. Infection of 2D cultures of neonatal rat ventricular myocytes with WT and mutant channels increased conduction velocity compared with noninfected cells. PKA stimulation significantly increased peak INa and conduction velocity of WT but not mutant channels. Oxidant stress inhibits cardiac INa; WT and mutant INa decreases with the intracellular application of reduced nicotinamide adenine dinucleotide (NADH), an effect that is reversed by PKA stimulation in WT but not in R526H or S528A channels.
conclusionsWe identified a family with BrS and an SCN5A mutation in a PKA consensus phosphorylation site. The BrS mutation R526H is associated with a reduction in the basal level of INa and a failure of PKA stimulation to augment the current that may contribute to the predisposition to arrhythmias in patients with BrS, independent of the precipitants.
Indexed as
Identifiers
What OpenQuestion holds
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.