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2-hydroxyoleic acid affects cardiomyocyte [Ca2+]i transient and contractility in a region-dependent manner.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2008 Apr; Vol. 294 (4), pp. H1948-55. Date of Electronic Publication: 2008 Feb 22. - Publication Year :
- 2008
-
Abstract
- Monounsaturated fatty acids such as oleic acid are cardioprotective, modify the physicochemical properties of cardiomyocyte membranes, and affect the electrical stability of these cells by regulating the conductance of ion channels. We have designed a nonhydrolysable oleic acid derivative, 2-hydroxyoleic acid (2-OHOA), which regulates membrane lipid structure and cell signaling, resulting in beneficial cardiovascular effects. We previously demonstrated that 2-OHOA induces PKA activation and PKCalpha translocation to the membrane; both pathways are thought to regulate transient outward K(+) current (I(to)) depending on the stimulus and the species used. This study was designed to investigate the effect of 2-OHOA on isolated cardiomyocytes. We examined the dose- and time-dependent effect of 2-OHOA on cytosolic Ca(2+) concentration ([Ca(2+)](i)) transient and contraction of myocytes isolated from different parts of the rat ventricular myocardium. Although this drug had no effect on [Ca(2+)](i) transient and cell shortening in myocytes isolated from the septum, it increased (up to 95%) [Ca(2+)](i) transient and cell shortening in subpopulations of myocytes from the right and left ventricles. The pattern of the effects of 2-OHOA was similar to that observed following the application of the I(to) blocker 4-aminopyridine, suggesting that the drug may act on this channel. Unlike the effect of 2-OHOA on [Ca(2+)](i) transient and cell shortening, PKCalpha translocation to membranes was not region specific. Thus 2-OHOA-induced effects on [Ca(2+)](i) transients and cell shortening are likely related to reductions in I(to) function, but PKCalpha translocation does not seem to play a role. The present results indicate that 2-OHOA selectively increases myocyte inotropic responsiveness, which could underlie its beneficial cardiovascular effects.
- Subjects :
- 4-Aminopyridine pharmacology
Animals
Cell Membrane drug effects
Cell Membrane metabolism
Cell Size drug effects
Cell Survival drug effects
Cells, Cultured
Cytosol drug effects
Cytosol metabolism
Dose-Response Relationship, Drug
Heart Septum drug effects
Heart Septum metabolism
Heart Ventricles drug effects
Heart Ventricles metabolism
Male
Myocytes, Cardiac enzymology
Myocytes, Cardiac metabolism
Potassium Channel Blockers pharmacology
Potassium Channels drug effects
Potassium Channels metabolism
Protein Kinase C-alpha metabolism
Protein Transport
Rats
Rats, Sprague-Dawley
Time Factors
Calcium Signaling drug effects
Cardiotonic Agents pharmacology
Myocardial Contraction drug effects
Myocytes, Cardiac drug effects
Oleic Acids pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0363-6135
- Volume :
- 294
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 18296566
- Full Text :
- https://doi.org/10.1152/ajpheart.01209.2007