PMID: 12064599Jun 18, 2002Paper

Protein kinase Calpha mediates the effect of antiarrhythmic peptide on gap junction conductance

Cell Communication & Adhesion
Stefan DheinLioudmila Polontchouk

Abstract

We investigated the effects of the antiarrhythmic peptide AAP10 (GAG-4Hyp-PY-CONH2, 50 nM) on pairs of adult guinea pig cardiomyocytes and on pairs of HeLa-cells transfected with rat connexin43 (Cx43). Using double cell voltage clamp technique in cardiomyocytes under control conditions, gap junction conductance (Gj) steadily decreased (by -0.3 to -0.4 nS/min). In contrast, 50 nM AAP10 significantly enhanced Gj (by +0.22 to +0.29 nS/min). This effect of AAP10 could be significantly antagonized by bisindolylmaleimide I (BIM), and by the protein kinase C (PKC) subtype-specific inhibitors HBDDE (PKCgamma and -alpha) and CGP 54345 (PKCalpha). In HeLa-Cx43 cells we found similar electrophysiological effects of AAP10. For further analysis, we incubated HeLa-Cx43 cells with [32P]orthophosphate (0.05 mCi/ml) for 4 h at 37 degrees C followed by addition of 50 nM AAP10 for 15 min. We found that incorporation of 32P into Cx43 was significantly enhanced in the presence of AAP10, which was completely inhibited in presence of BIM. PKC enzyme-linked immunosorbent assay (ELISA) revealed significant activation of PKC by AAP10 in HeLa-Cx43 cells, which could be inhibited by HBDDE and CGP 54345. Finally, a binding study using [14C]-AAP10 as radiol...Continue Reading

References

Sep 1, 1987·Chemical & Pharmaceutical Bulletin·Y KohamaK Yokoyama
Jan 7, 1994·Journal of Medicinal Chemistry·Y KashiwadaK H Lee
Aug 1, 1996·Journal of Bioenergetics and Biomembranes·A F LauP D Lampe
May 26, 1997·European Journal of Pharmacology·A MüllerS Dhein
Jul 1, 1997·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·J Hofmann

❮ Previous
Next ❯

Citations

Mar 28, 2009·Naunyn-Schmiedeberg's Archives of Pharmacology·Jennifer A EastonPatricia E M Martin
Nov 28, 2009·Naunyn-Schmiedeberg's Archives of Pharmacology·Stefan DheinFriedrich-Wilhelm Mohr
Sep 12, 2012·Naunyn-Schmiedeberg's Archives of Pharmacology·Joanna JozwiakStefan Dhein
Jul 21, 2007·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Rong WangLin Wang
Sep 10, 2002·Peptides·Stefan Dhein
Jan 13, 2012·Proceedings of the National Academy of Sciences of the United States of America·Dennis RottlaenderUta C Hoppe
Aug 2, 2008·Circulation Research·Rebecca LewandowskiMario Delmar
Dec 19, 2003·Cell Communication & Adhesion·Stefan DheinFriedrich-Wilhelm Mohr
Sep 5, 2009·Journal of Molecular and Cellular Cardiology·John A JansenHarold V M van Rijen
Aug 31, 2007·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Shi-Wei ZhangLiang Liu
Sep 12, 2007·Basic & Clinical Pharmacology & Toxicology·Anne Louise KjølbyeJørgen S Petersen
Jan 27, 2011·British Journal of Pharmacology·Elke De VuystLuc Leybaert
Nov 2, 2014·Cell and Tissue Research·Pier D Lambiase, Andrew Tinker
Apr 7, 2017·Journal of Cardiovascular Pharmacology and Therapeutics·Laura A HundahlThomas Jespersen
May 13, 2006·Circulation Research·Junko ShibayamaMario Delmar
Sep 22, 2017·Pharmacological Reviews·Luc LeybaertRainer Schulz

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anti-Arrhythmic Drug Therapies

Anti-arrhythmic drugs are used to prevent abnormal heart rhythms. These medications are used in conditions including, ventricular tachycardia, ventricular fibrillation and atrial fibrillation. Discover the latest research on anti-arrhythmic drug therapies here.

Antiarrhythmic Agents: Mechanisms of Action

Understanding the mechanism of action of antiarrhythmic agents is essential in developing new medications as treatment of cardiac arrhythmias is currently limited by the reduced availability of safe and effective drugs. Discover the latest research on Antiarrhythmic Agents: Mechanism of Action here.

Arrhythmia

Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.