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Increased basal contractility of cardiomyocytes overexpressing protein kinase Cε and blunted positive inotropic response to endothelin-1
- Source :
- Cardiovascular Research. 50:486-494
- Publication Year :
- 2001
- Publisher :
- Oxford University Press (OUP), 2001.
-
Abstract
- 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.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.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% (P0.05 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.Specific overexpression of PKC epsilon in rabbit ventricular myocytes increases basal myocyte contractility and [Ca2+]i transients, and modifies their responsiveness to ET-1.
- Subjects :
- medicine.medical_specialty
Cardiotonic Agents
Physiology
Heart Ventricles
Genetic Vectors
Cell Culture Techniques
030204 cardiovascular system & hematology
Biology
Adenoviridae
Contractility
03 medical and health sciences
Basal (phylogenetics)
0302 clinical medicine
Physiology (medical)
Internal medicine
medicine
Animals
Myocyte
Kinase activity
Protein kinase A
Protein Kinase C
Protein kinase C
030304 developmental biology
0303 health sciences
Dose-Response Relationship, Drug
Endothelin-1
Myocardium
Cardiac myocyte
Gene Transfer Techniques
Myocardial Contraction
Endothelin 1
3. Good health
Endocrinology
Calcium
Rabbits
Cardiology and Cardiovascular Medicine
Subjects
Details
- ISSN :
- 00086363
- Volume :
- 50
- Database :
- OpenAIRE
- Journal :
- Cardiovascular Research
- Accession number :
- edsair.doi.dedup.....1cb96a4d5d090548ba747559d17e4af5