ArticleThe Journal of clinical investigation2021
Cx43 hemichannel microdomain signaling at the intercalated disc enhances cardiac excitability.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Therapeutic Potential of Exosome for Cardiac Arrhythmia: A Systematic Review of Preclinical Evidence.Stem cell reviews and reports · 2025Pooled it
- Reduced Cx43 S-nitrosylation protects against cardiac stress-induced arrhythmias and myocardial injury in Duchenne muscular dystrophy.Cardiovascular research · 2026Article
- Gut microbiota-activated PLCγ2 monocytes drive atrial fibrillation.Nature communications · 2026Article
- Voltage-Dependent Ion Channels in Vascular Endothelial Cells: An Unexpected Signaling Pathway in Non-Excitable Cells.Biomedicines · 2026Review
- COeLife · 2026Article
- Cardiac Impulse Propagation: An Integrated View.JACC. Basic to translational science · 2026Review
- Phospho-mimic βIII-tubulin rescues microtubule and cardiac defects in Duchenne muscular dystrophy mice.Journal of molecular and cellular cardiology · 2026Article
- Bioactive Magnesium Silicate Activating Myocardial Energy Metabolism For Infarcted Myocardium Repair.Exploration (Beijing, China) · 2026Article
- Ephaptic coupling and the source-sink effect of cardiac conduction.The Journal of physiology · 2026Article
- HIV heart inflammation is mediated by HIV infected myeloid cells, HIV-tat secretion, and aberrant function of Connexin43-containing channels.Scientific reports · 2026Article
- Silicate biomaterials-based multicellular scaffolds with specific cellular spatial distribution for infarcted myocardium repair.Bioactive materials · 2026Article
- Destabilized calcium dynamics visualized using the genetically-coded probe GCaMPJ in intact hearts of Calstabin2-null mice.Frontiers in physiology · 2026Article
- Connexin 43 in Pathophysiology of Cardiac Diseases: From Molecular Mechanisms to Therapeutic Strategies.Physiological research · 2025Review
- FGF13 Regulates VGSC-Independent Cardiomyocyte Impulse Propagation via Cx43 Trafficking.Circulation research · 2025Article
- Endothelial TRPV4-Cx43 signalling complex regulates vasomotor tone in resistance arteries.The Journal of physiology · 2025Article
- Cardiac resident macrophages in cardiovascular disease: from physiology to pathology.Heart (British Cardiac Society) · 2025Review
- Research progress of connexin 43 in cardiovascular diseases.Frontiers in cardiovascular medicine · 2025Review
- Endothelial TRPV4/Cx43 Signaling Complex Regulates Vasomotor Tone in Resistance Arteries.bioRxiv : the preprint server for biology · 2024Article
- Calcium Regulation of Connexin Hemichannels.International journal of molecular sciences · 2024Review
- E-cardiac patch to sense and repair infarcted myocardium.Nature communications · 2024Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cx43, a major cardiac connexin, forms precursor hemichannels that accrue at the intercalated disc to assemble as gap junctions. While gap junctions are crucial for electrical conduction in the heart, little is known about the potential roles of hemichannels. Recent evidence suggests that inhibiting Cx43 hemichannel opening with Gap19 has antiarrhythmic effects. Here, we used multiple electrophysiology, imaging, and super-resolution techniques to understand and define the conditions underlying Cx43 hemichannel activation in ventricular cardiomyocytes, their contribution to diastolic Ca2+ release from the sarcoplasmic reticulum, and their impact on electrical stability. We showed that Cx43 hemichannels were activated during diastolic Ca2+ release in single ventricular cardiomyocytes and cardiomyocyte cell pairs from mice and pigs. This activation involved Cx43 hemichannel Ca2+ entry and coupling to Ca2+ release microdomains at the intercalated disc, resulting in enhanced Ca2+ dynamics. Hemichannel opening furthermore contributed to delayed afterdepolarizations and triggered action potentials. In single cardiomyocytes, cardiomyocyte cell pairs, and arterially perfused tissue wedges from failing human hearts, increased hemichannel activity contributed to electrical instability compared with nonfailing rejected donor hearts. We conclude that microdomain coupling between Cx43 hemichannels and Ca2+ release is a potentially novel, targetable mechanism of cardiac arrhythmogenesis in heart failure.
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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.