ReviewNaunyn-Schmiedeberg's archives of pharmacology2010
Improving cardiac gap junction communication as a new antiarrhythmic mechanism: the action of antiarrhythmic peptides.
Review in Naunyn-Schmiedeberg's archives of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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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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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.
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Who cites it
37 citing papers in PubMed, 86 citations in OpenAlex.
- A bibliometric study of the most-cited research articles and reviews in Naunyn-Schmiedeberg's Archives of Pharmacology (1969-2024).Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Acute ischaemia and gap junction modulation modify propagation patterns across Purkinje-myocardial junctions.Frontiers in physiology · 2025Article
- Connexin43, A Promising Target to Reduce Cardiac Arrhythmia Burden in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2024Review
- Review
- Connexin hemichannels as candidate targets for cardioprotective and anti-arrhythmic treatments.The Journal of clinical investigation · 2023Review
- New Strategies for the Treatment of Atrial Fibrillation.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Peptidic Connexin43 Therapeutics in Cardiac Reparative Medicine.Journal of cardiovascular development and disease · 2021Review
- Connexins in the Heart: Regulation, Function and Involvement in Cardiac Disease.International journal of molecular sciences · 2021Review
- Danegaptide Prevents TGFβ1-Induced Damage in Human Proximal Tubule Epithelial Cells of the Kidney.International journal of molecular sciences · 2021Article
- Attenuating loss of cardiac conduction during no-flow ischemia through changes in perfusate sodium and calcium.American journal of physiology. Heart and circulatory physiology · 2020Article
- Prevention of connexin-43 remodeling protects against Duchenne muscular dystrophy cardiomyopathy.The Journal of clinical investigation · 2020Article
- Obesity-associated alterations in cardiac connexin-43 and PKC signaling are attenuated by melatonin and omega-3 fatty acids in female rats.Molecular and cellular biochemistry · 2019Article
- Gap junctional communication is involved in differentiation of osteoclasts from bone marrow and peripheral blood monocytes.Heliyon · 2018Article
- Cardiac Innervation and the Autonomic Nervous System in Sudden Cardiac Death.Cardiac electrophysiology clinics · 2017Review
- Connexins in Cardiovascular and Neurovascular Health and Disease: Pharmacological Implications.Pharmacological reviews · 2017Review
- Chronic inhibition of fatty acid amide hydrolase by URB597 produces differential effects on cardiac performance in normotensive and hypertensive rats.British journal of pharmacology · 2017Article
- Phosphorylation at Connexin43 Serine-368 Is Necessary for Myocardial Conduction During Metabolic Stress.Journal of cardiovascular electrophysiology · 2016Article
- Role of Calcium-activated Potassium Channels in Atrial Fibrillation Pathophysiology and Therapy.Journal of cardiovascular pharmacology · 2015Review
- Cardiomyocyte protein trafficking: Relevance to heart disease and opportunities for therapeutic intervention.Trends in cardiovascular medicine · 2015Review
- Specific Cx43 phosphorylation events regulate gap junction turnover in vivo.FEBS letters · 2014Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Co-ordinated electrical activation of the heart is maintained by intercellular coupling of cardiomyocytes via gap junctional channels located in the intercalated disks. These channels consist of two hexameric hemichannels, docked to each other, provided by either of the adjacent cells. Thus, a complete gap junction channel is made from 12 protein subunits, the connexins. While 21 isoforms of connexins are presently known, cardiomyocytes typically are coupled by Cx43 (most abundant), Cx40 or Cx45. Some years ago, antiarrhythmic peptides were discovered and synthesised, which were shown to increase macroscopic gap junction conductance (electrical coupling) and enhance dye transfer (metabolic coupling). The lead substance of these peptides is AAP10 (H-Gly-Ala-Gly-Hyp-Pro-Tyr-CONH(2)), a peptide with a horseshoe-like spatial structure as became evident from two-dimensional nuclear magnetic resonance studies. A stable D: -amino-acid derivative of AAP10, rotigaptide, as well as a non-peptide analogue, gap-134, has been developed in recent years. Antiarrhythmic peptides act on Cx43 and Cx45 gap junctions but not on Cx40 channels. AAP10 has been shown to enhance intercellular communication in rat, rabbit and human cardiomyocytes. Antiarrhythmic peptides are effective against ventricular tachyarrhythmias, such as late ischaemic (type IB) ventricular fibrillation, CaCl(2) or aconitine-induced arrhythmia. Interestingly, the effect of antiarrhythmic peptides is higher in partially uncoupled cells and was shown to be related to maintained Cx43 phosphorylation, while arrhythmogenic conditions like ischaemia result in Cx43 dephosphorylation and intercellular decoupling. It is still a matter of debate whether these drugs also act against atrial fibrillation. The present review outlines the development of this group of peptides and derivatives, their mode of action and molecular mechanisms, and discusses their possible therapeutic potential.
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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.