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This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/H1948    most recent 01209.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Borchert, G. H. Articles by Escriba, P. V. PubMed PubMed Citation Articles by Borchert, G. H. Articles by Escriba, P. V.

2-Hydroxyoleic acid affects cardiomyocyte [Ca²⁺]_i transient and contractility in a region-dependent manner

¹Laboratory of Molecular and Cellular Biomedicine, University of the Balearic Islands, Palma de Mallorca, Spain; ²Institute of Physiology, Academy of Sciences of the Czech Republic and Centre for Cardiovascular Research, Prague, Czech Republic; ³Department of Physiology and Medicine, University of Toronto, Heart and Stroke/Richard-Lewar-Centre of Excellence, Toronto, Canada; and ⁴Department of Physiology, The University of Hong Kong, Hong Kong, China

Submitted 18 October 2007 ; accepted in final form 20 February 2008

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 PKC 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 Ca²⁺ concentration ([Ca²⁺]_i) transient and contraction of myocytes isolated from different parts of the rat ventricular myocardium. Although this drug had no effect on [Ca²⁺]_i transient and cell shortening in myocytes isolated from the septum, it increased (up to 95%) [Ca²⁺]_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 [Ca²⁺]_i transient and cell shortening, PKC translocation to membranes was not region specific. Thus 2-OHOA-induced effects on [Ca²⁺]_i transients and cell shortening are likely related to reductions in I_to function, but PKC 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.

calcium; contractile function; fatty acid; protein kinase C; signal transduction