Skip Navigation

Cardiovascular Research 2001 50(3):486-494; doi:10.1016/S0008-6363(01)00225-5
© 2001 by European Society of Cardiology
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Baudet, S.
Right arrow Articles by Prestle, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Baudet, S.
Right arrow Articles by Prestle, J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2001, European Society of Cardiology

Increased basal contractility of cardiomyocytes overexpressing protein kinase C{epsilon} and blunted positive inotropic response to endothelin-1

Stéphane Baudet1,a, Jutta Weisserb, Anita P Janssenb, Kathrin Beulicha, Ursula Bieligka, Burkert Pieskeb, Jacques Noireaudc, Paul M.L Janssenb, Gerd Hasenfussb and Juergen Prestleb,*

aDepartment of Cardiology and Angiology, University of Freiburg, D-79106 Freiburg, Germany
bGeorg-August-Universitaet Goettingen, Zentrum Innere Medizin, Department of Cardiology and Pneumology, Robert-Koch-Strasse 40, D-37075 Goettingen, Germany
cINSERM U533, F-44035 Nantes Cedex 01, France

* Corresponding author. Tel.: +49-551-396-380; fax: +49-551-392-953 stephane.baudet{at}intervet.com prestle{at}med.uni-goettingen.de

Objective: Protein kinase C (PKC) is thought to be involved in the regulation of the mammalian cardiac excitation–contraction coupling process by vasoactive peptides like endothelin-1 (ET-1). However, the demonstration of a causal link between activation of specific PKC isoforms and the increase in contractility mediated by ET-1 is still inferential. Methods: By means of adenovirus-mediated gene transfer, we specifically overexpressed PKC{epsilon} in cultured adult rabbit ventricular myocytes (Ad-PKC{epsilon}). Myocyte shortening and [Ca2+]i transients under basal and ET-1-stimulated conditions were measured in Ad-PKC{epsilon} and Ad-LacZ control transfected cells. Results: Infection with Ad-PKC{epsilon} resulted in a strong, virus dose-dependent increase in PKC{epsilon} protein levels, whereas protein expression of other PKC isoforms remained unchanged. Using a multiplicity of infection of 100 plaque-forming units/myocyte, basal and cofactor-dependent PKC{epsilon} kinase activity was increased 28- and 90-fold, respectively, when compared to control. Myocyte basal fractional shortening and [Ca2+]i transient amplitude were both increased by 21% (P<0.05 each) in Ad-PKC{epsilon} transfected myocytes when compared to Ad-LacZ transfected control myocytes. The positive inotropic effect of ET-1 in control myocytes was markedly blunted in PKC{epsilon}-overexpressing myocytes. Conclusion: Specific overexpression of PKC{epsilon} in rabbit ventricular myocytes increases basal myocyte contractility and [Ca2+]i transients, and modifies their responsiveness to ET-1.

KEYWORDS Contractile function; e–c Coupling; Endothelins; Gene therapy; Myocytes; Protein kinases; Signal transduction

1 Present address: Stéphane Baudet, Intervet Pharma R&D, Internal Medicine II, BP 67131, F-49071 Beaucouzé Cedex, France.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.