ArticleJCI insight2018
Brugada syndrome trafficking-defective Nav1.5 channels can trap cardiac Kir2.1/2.2 channels.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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
31 citing papers in PubMed, 50 citations in OpenAlex.
- Repurposing polyamines to prevent life-threatening arrhythmias in Short QT Syndrome type 3.Nature communications · 2026Article
- Electrophysiological Modeling and Molecular Dynamics Simulations of Cardiac Sodium Channels in Brugada Syndrome.BioMed research international · 2026Article
- Consequences of Right Heart Disease for Cardiac Electrophysiology and Arrhythmias: Cellular and Structural Mechanisms.CJC open · 2025Review
- Propionic Acidemia-Induced Proarrhythmic Electrophysiological Alterations in Human iPSC-Derived Cardiomyocytes.Journal of inherited metabolic disease · 2025Article
- Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome.Cell discovery · 2025Review
- The Role of Human-Induced Pluripotent Stem Cells in Studying Cardiac Channelopathies.International journal of molecular sciences · 2024Review
- The Kir2.1E299V mutation increases atrial fibrillation vulnerability while protecting the ventricles against arrhythmias in a mouse model of short QT syndrome type 3.Cardiovascular research · 2024Article
- Variable Penetrance and Expressivity of a Rare Pore Loss-of-Function Mutation (p.L889V) of Nav1.5 Channels in Three Spanish Families.International journal of molecular sciences · 2024Article
- Extracellular Kir2.1Circulation research · 2024Article
- Stem cell models of inherited arrhythmias.Nature cardiovascular research · 2024Review
- Article
- Extracellular cysteine disulfide bond break at Cys122 disrupts PIPbioRxiv : the preprint server for biology · 2023Article
- Molecular stratification of arrhythmogenic mechanisms in the Andersen Tawil syndrome.Cardiovascular research · 2023Article
- Maturation of hiPSC-derived cardiomyocytes promotes adult alternative splicing of SCN5A and reveals changes in sodium current associated with cardiac arrhythmia.Cardiovascular research · 2023Article
- Chronic Propafenone Application Increases Functional KPharmaceuticals (Basel, Switzerland) · 2023Article
- A Cantú syndrome mutation produces dual effects on KATP channels by disrupting ankyrin B regulation.The Journal of general physiology · 2023Article
- Empagliflozin and Dapagliflozin Increase NaCells · 2022Article
- Article
- Absolute Quantification of Nav1.5 Expression by Targeted Mass Spectrometry.International journal of molecular sciences · 2022Article
- Cardiomyocyte Microtubules: Control of Mechanics, Transport, and Remodeling.Annual review of physiology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 3 institutions in 2 countries.
Funding
Abstract
Cardiac Nav1.5 and Kir2.1-2.3 channels generate Na (INa) and inward rectifier K (IK1) currents, respectively. The functional INa and IK1 interplay is reinforced by the positive and reciprocal modulation between Nav15 and Kir2.1/2.2 channels to strengthen the control of ventricular excitability. Loss-of-function mutations in the SCN5A gene, which encodes Nav1.5 channels, underlie several inherited arrhythmogenic syndromes, including Brugada syndrome (BrS). We investigated whether the presence of BrS-associated mutations alters IK1 density concomitantly with INa density. Results obtained using mouse models of SCN5A haploinsufficiency, and the overexpression of native and mutated Nav1.5 channels in expression systems - rat ventricular cardiomyocytes and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) - demonstrated that endoplasmic reticulum (ER) trafficking-defective Nav1.5 channels significantly decreased IK1, since they did not positively modulate Kir2.1/2.2 channels. Moreover, Golgi trafficking-defective Nav1.5 mutants produced a dominant negative effect on Kir2.1/2.2 and thus an additional IK1 reduction. Moreover, ER trafficking-defective Nav1.5 channels can be partially rescued by Kir2.1/2.2 channels through an unconventional secretory route that involves Golgi reassembly stacking proteins (GRASPs). Therefore, cardiac excitability would be greatly affected in subjects harboring Nav1.5 mutations with Golgi trafficking defects, since these mutants can concomitantly trap Kir2.1/2.2 channels, thus unexpectedly decreasing IK1 in addition to INa.
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.