ArticleNaunyn-Schmiedeberg's archives of pharmacology2008
Local effects and mechanisms of antiarrhythmic peptide AAP10 in acute regional myocardial ischemia: electrophysiological and molecular findings.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 48 citations in OpenAlex.
- Mechanisms of Connexin Regulating Peptides.International journal of molecular sciences · 2021Review
- Review
- 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
- Connexin 43 Functions as a Positive Regulator of Stem Cell Differentiation into Definitive Endoderm and Pancreatic Progenitors.iScience · 2019Article
- Interaction of α Carboxyl Terminus 1 Peptide With the Connexin 43 Carboxyl Terminus Preserves Left Ventricular Function After Ischemia-Reperfusion Injury.Journal of the American Heart Association · 2019Article
- Intercalated discs: cellular adhesion and signaling in heart health and diseases.Heart failure reviews · 2019Review
- Connexins in Cardiovascular and Neurovascular Health and Disease: Pharmacological Implications.Pharmacological reviews · 2017Review
- The gap junction modifier ZP1609 decreases cardiomyocyte hypercontracture following ischaemia/reperfusion independent from mitochondrial connexin 43.British journal of pharmacology · 2017Article
- Arrhythmogenic effects by local left ventricular stretch: effects of flecainide and streptomycin.Naunyn-Schmiedeberg's archives of pharmacology · 2014Article
- Specific Cx43 phosphorylation events regulate gap junction turnover in vivo.FEBS letters · 2014Review
- Remodeling of cardiac passive electrical properties and susceptibility to ventricular and atrial arrhythmias.Frontiers in physiology · 2014Review
- The antiarrhythmic dipeptide ZP1609 (danegaptide) when given at reperfusion reduces myocardial infarct size in pigs.Naunyn-Schmiedeberg's archives of pharmacology · 2013Article
- Myocardial impulse propagation is impaired in right ventricular tissue of Zucker diabetic fatty (ZDF) rats.Cardiovascular diabetology · 2013Article
- On the different roles of AT1 and AT2 receptors in stretch-induced changes of connexin43 expression and localisation.Pflugers Archiv : European journal of physiology · 2012Article
- Desipramine prevents cardiac gap junction uncoupling.Naunyn-Schmiedeberg's archives of pharmacology · 2012Article
- The connexin43 carboxyl terminus and cardiac gap junction organization.Biochimica et biophysica acta · 2012Review
- ZP123 reduces energy required for defibrillation by preventing connexin43 remodeling during prolonged ventricular fibrillation in swine.Texas Heart Institute journal · 2012Article
- Pharmacological modulation of connexin-formed channels in cardiac pathophysiology.British journal of pharmacology · 2011Review
- A peptide mimetic of the connexin43 carboxyl terminus reduces gap junction remodeling and induced arrhythmia following ventricular injury.Circulation research · 2011Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Previously, it was shown that antiarrhythmic peptides and our lead substance AAP10 enhance electrical intercellular communication via gap junctions. Now, we wanted to elucidate whether AAP10 acts preferably in the ischemic area and the molecular mechanism of this peptide. Seventeen rabbit hearts were isolated, perfused according to Langendorff, and submitted to 30-min local ischemia by LAD occlusion with/without AAP10 (50 nM). Electrophysiology was assessed by 256 channel epicardial mapping. Finally, the ischemic zone, border zone, and non-ischemic zone were excised, and the cardiac gap junction protein connexin43 (Cx43), its phosphorylation state, and the distribution at the polar and lateral membrane of cardiomyocytes were determined by Western blot and immunofluorescence. Ischemia led to a decrease in activation recovery interval (ARI) homogeneity, which could be completely prevented by AAP10. Moreover, ischemia-induced activation wave slowing in the ischemic border zone was antagonized by AAP10. In ischemic center and border zone, but not in the non-ischemic area, (phospho-Cx43/dephospho-Cx43)-ratio decreased. This was also significantly antagonized by AAP10. Serine 368 was identified as one phosphorylation site for the activity of AAP10. In the non-ischemic area, AAP10 had no influence on Cx43 phosphorylation state. Interestingly, ischemia led to a loss of Cx43 from the cell poles and lateral sides in the ischemic area and border zone. AAP10 completely prevented the ischemia-induced decrease in polar Cx43 presence. In the ischemic area, AAP10 prevents from ischemia-induced Cx43 dephosphorylation and loss of Cx43 from the gap junction at cell poles and in parallel prevents the decrease in ARI homogeneity and attenuates ischemia-induced slowing of activation wave propagation. The AAP10 action seems confined to the ischemic area.
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