ArticleCirculation research2008
RXP-E: a connexin43-binding peptide that prevents action potential propagation block.
Article in Circulation research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Intracellular Redistribution of Left Ventricular Connexin 43 Contributes to the Remodeling of Electrical Properties of the Heart in Insulin-resistant Elderly Rats.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2022Article
- Connexins and Disease.Cold Spring Harbor perspectives in biology · 2018Review
- Connexins in Cardiovascular and Neurovascular Health and Disease: Pharmacological Implications.Pharmacological reviews · 2017Review
- Cardiac to cancer: connecting connexins to clinical opportunity.FEBS letters · 2014Review
- Paracrine signaling through plasma membrane hemichannels.Biochimica et biophysica acta · 2013Review
- Connexin mimetic peptides inhibit Cx43 hemichannel opening triggered by voltage and intracellular Ca2+ elevation.Basic research in cardiology · 2012Article
- Manipulating connexin communication channels: use of peptidomimetics and the translational outputs.The Journal of membrane biology · 2012Review
- Gap junctions.Comprehensive Physiology · 2012Review
- SkM1 and Cx32 improve conduction in canine myocardial infarcts yet only SkM1 is antiarrhythmic.Cardiovascular research · 2012Article
- Novel molecular targets for atrial fibrillation therapy.Nature reviews. Drug discovery · 2012Review
- Glycogen synthase kinase 3β transfers cytoprotective signaling through connexin 43 onto mitochondrial ATP-sensitive K+ channels.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- GATA6 reporter gene reveals myocardial phenotypic heterogeneity that is related to variations in gap junction coupling.American journal of physiology. Heart and circulatory physiology · 2011Article
- Plakophilin-2 and the migration, differentiation and transformation of cells derived from the epicardium of neonatal rat hearts.Cell communication & adhesion · 2011Article
- Pharmacological modulation of connexin-formed channels in cardiac pathophysiology.British journal of pharmacology · 2011Review
- Expression of skeletal muscle sodium channel (Nav1.4) or connexin32 prevents reperfusion arrhythmias in murine heart.Cardiovascular research · 2011Article
- Design and characterization of the first peptidomimetic molecule that prevents acidification-induced closure of cardiac gap junctions.Heart rhythm · 2010Article
- Cx43 CT domain influences infarct size and susceptibility to ventricular tachyarrhythmias in acute myocardial infarction.Cardiovascular research · 2009Article
- Novel pharmacophores of connexin43 based on the "RXP" series of Cx43-binding peptides.Circulation research · 2009Article
- Connexins participate in the initiation and progression of atherosclerosis.Seminars in immunopathology · 2009Review
- Turning on/off the dome in phase 2 reentry: the switching wave hypothesis.Heart rhythm · 2009Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Gap junctions provide a low-resistance pathway for cardiac electric propagation. The role of GJ regulation in arrhythmia is unclear, partly because of limited availability of pharmacological tools. Recently, we showed that a peptide called "RXP-E" binds to the carboxyl terminal of connexin43 and prevents chemically induced uncoupling in connexin43-expressing N2a cells. Here, pull-down experiments show RXP-E binding to adult cardiac connexin43. Patch-clamp studies revealed that RXP-E prevented heptanol-induced and acidification-induced uncoupling in pairs of neonatal rat ventricular myocytes. Separately, RXP-E was concatenated to a cytoplasmic transduction peptide (CTP) for cytoplasmic translocation (CTP-RXP-E). The effect of RXP-E on action potential propagation was assessed by high-resolution optical mapping in monolayers of neonatal rat ventricular myocytes, containing approximately 20% of randomly distributed myofibroblasts. In contrast to control experiments, when heptanol (2 mmol/L) was added to the superfusate of monolayers loaded with CTP-RXP-E, action potential propagation was maintained, albeit at a slower velocity. Similarly, intracellular acidification (pH(i) 6.2) caused a loss of action potential propagation in control monolayers; however, propagation was maintained in CTP-RXP-E-treated cells, although at a slower rate. Patch-clamp experiments revealed that RXP-E did not prevent heptanol-induced block of sodium currents, nor did it alter voltage dependence or amplitude of Kir2.1/Kir2.3 currents. RXP-E is the first synthetic molecule known to: (1) bind cardiac connexin43; (2) prevent heptanol and acidification-induced uncoupling of cardiac gap junctions; and (3) preserve action potential propagation among cardiac myocytes. RXP-E can be used to characterize the role of gap junctions in the function of multicellular systems, including the heart.
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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.