SynthesisCardiovascular research2021
Co-expression of calcium and hERG potassium channels reduces the incidence of proarrhythmic events.
Synthesis in Cardiovascular research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
- Comparative transcriptomics analysis of histone deacetylases, transcription factors, and ion channel genes in human iPSC-cardiomyocytes vs. the adult human heart.Journal of precision medicine (Amsterdam, Netherlands) · 2026Article
- Can in silico models predict drug-induced cardiac risk in vulnerable populations?Toxicology reports · 2026Article
- Role of natural inter-individual variability in the different penetrance of congenital long QT syndromes (LQTS) types 1 and 2: an in silico approach.Scientific reports · 2026Article
- Interplay between variability in intrinsic cellular properties and heart failure-associated remodeling in a simulated population with human heart failure.Journal of molecular and cellular cardiology · 2026Article
- Comparative transcriptomics analysis of histone deacetylases, transcription factors, and ion channel genes in human iPSC-cardiomyocytes vs. the adult human heart.bioRxiv : the preprint server for biology · 2026Article
- Calcium Homeostatic Feedback Control Predicts Atrial Fibrillation Initiation, Remodeling, and Progression.JACC. Clinical electrophysiology · 2025Article
- Electrophysiological tolerance: a new concept for understanding the electrical stability of the heart.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2024Review
- Development of an Absolute Quantification Method for hERG Using PRM with Single Isotopologue in-Sample Calibration.ACS omega · 2024Article
- Relationship between ion currents and membrane capacitance in canine ventricular myocytes.Scientific reports · 2024Article
- Assessing drug safety by identifying the axis of arrhythmia in cardiomyocyte electrophysiology.eLife · 2023Article
- Targeted activation of human ether-à-go-go-related gene channels rescues electrical instability induced by the R56Q+/- long QT syndrome variant.Cardiovascular research · 2023Article
- Pairwise biosynthesis of ion channels stabilizes excitability and mitigates arrhythmias.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Diversity of cells and signals in the cardiovascular system.The Journal of physiology · 2023Article
- Initiation of ventricular arrhythmia in the acquired long QT syndrome.Cardiovascular research · 2023Article
- Modeling incomplete penetrance in long QT syndrome type 3 through ion channel heterogeneity: an in silico population study.American journal of physiology. Heart and circulatory physiology · 2023Article
- Electrophysiological heterogeneity in large populations of rabbit ventricular cardiomyocytes.Cardiovascular research · 2022Article
- Sex-dependent transcription of cardiac electrophysiology and links to acetylation modifiers based on the GTEx database.Frontiers in cardiovascular medicine · 2022Article
- Computational models of atrial fibrillation: achievements, challenges, and perspectives for improving clinical care.Cardiovascular research · 2021Review
- Network Pharmacology-Based Systematic Analysis of Molecular Mechanisms of Dingji Fumai Decoction for Ventricular Arrhythmia.Evidence-based complementary and alternative medicine : eCAM · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsCardiac electrical activity is extraordinarily robust. However, when it goes wrong it can have fatal consequences. Electrical activity in the heart is controlled by the carefully orchestrated activity of more than a dozen different ion conductances. While there is considerable variability in cardiac ion channel expression levels between individuals, studies in rodents have indicated that there are modules of ion channels whose expression co-vary. The aim of this study was to investigate whether meta-analytic co-expression analysis of large-scale gene expression datasets could identify modules of co-expressed cardiac ion channel genes in human hearts that are of functional importance. METHODS AND
resultsMeta-analysis of 3653 public human RNA-seq datasets identified a strong correlation between expression of CACNA1C (L-type calcium current, ICaL) and KCNH2 (rapid delayed rectifier K+ current, IKr), which was also observed in human adult heart tissue samples. In silico modelling suggested that co-expression of CACNA1C and KCNH2 would limit the variability in action potential duration seen with variations in expression of ion channel genes and reduce susceptibility to early afterdepolarizations, a surrogate marker for proarrhythmia. We also found that levels of KCNH2 and CACNA1C expression are correlated in human-induced pluripotent stem cell-derived cardiac myocytes and the levels of CACNA1C and KCNH2 expression were inversely correlated with the magnitude of changes in repolarization duration following inhibition of IKr.
conclusionMeta-analytic approaches of multiple independent human gene expression datasets can be used to identify gene modules that are important for regulating heart function. Specifically, we have verified that there is co-expression of CACNA1C and KCNH2 ion channel genes in human heart tissue, and in silico analyses suggest that CACNA1C-KCNH2 co-expression increases the robustness of cardiac electrical activity.
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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.