Submitted on October 18, 2007
Accepted on February 20, 2008
2-Hydroxyoleic acid affects cardiomyocyte [Ca2+]i transient and contractility in a region-dependent manner
Gudrun Hildegard Borchert1*, Mike Giggey2, Frantisek Kolar3, Tak Ming Wong4, Peter H. Backx5, and Pablo Vincent Escriba6
1 Laboratory of Molecular and Cellular Biology, University of the Balearic Island, Palma de Mallorca, Mallorca, Spain; Developmental Cardiology, Academy of Science of the Czech Republic, Praha 4, Czech Republic
2 Department of Physiology and Medicine,Heart and Stroke/Richard-Lewar-Centre of Excellence, University of Toronto, Toronto, Canada
3 Developmental Cardiology, Institute of Physiology AS CR, Prague 4, Czech Republic
4 Deapartment of Physiology, The University of Hong Kong, Hong Kong, China
5 Heart and Stroke, Richard Lewar Ctr, University of Toronto, Toronto, Canada
6 Laboratory of Molecular and Cellular Biology, University of the Balearic Island, Palma de Mallorca, Mallorca, Spain
* To whom correspondence should be addressed. E-mail: GudrunHBorchert{at}compuserve.com.
Monounsaturated fatty acids such as oleic acid are cardioprotective, modify the physico-chemical properties of cardiomyocyte membranes and affect the electrical stability of these cells by regulating the conductance of ion channels. We have designed a non-hydrolyzable 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 Ito 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+]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 right and left ventricles. The pattern of the effects of 2-OHOA was similar to that observed following the application of the Ito blocker 4-aminopyridine, suggesting that the drug may act on this channel. Unlike the effect of 2-OHOA on [Ca2+]i transients 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 Ito 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.
