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Suppression of calcium sparks in rat ventricular myocytes and direct inhibition of sheep cardiac RyR channels by EPA, DHA and oleic acid

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dc.contributor.authorHonen, B.
dc.contributor.authorSaint, D.
dc.contributor.authorLaver, D.
dc.date.issued2003
dc.descriptionThe original publication is available at www.springerlink.com
dc.description.abstractThe anti-arrhythmic effects of long-chain polyunsaturated fatty acids (PUFAs) may be related to their ability to alter calcium handling in cardiac myocytes. We investigated the effect of eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) on calcium sparks in rat cardiac myocytes and the effects of these PUFAs and the monounsaturated oleic acid on cardiac calcium release channels (RyRs). Visualization of subcellular calcium concentrations in single rat ventricular myocytes showed that intensity of calcium sparks was reduced in the presence of EPA and DHA (15 µM). It was also found that calcium sparks decayed more quickly in the presence of EPA but not DHA. Sarcoplasmic vesicles containing RyRs were prepared from sheep hearts and RyR activity was determined by either [3H]ryanodine binding or by single-channel recording. Bilayers were formed from phosphatidylethanolamine and phosphatidylcholine dissolved in either n-decane or n-tetradecane. EPA inhibited [3H]ryanodine binding to RyRs in SR vesicles with K I = 40 µM. Poly- and mono-unsaturated free fatty acids inhibited RyR activity in lipid bilayers. EPA (cytosolic or luminal) inhibited RyRs with K I =32 µM and Hill coefficient, n 1 = 3.8. Inhibition was independent of the n-alkane solvent and whether RyRs were activated by ATP or Ca2+. DHA and oleic acid also inhibited RyRs, suggesting that free fatty acids generally inhibit RyRs at micromolar concentrations.
dc.description.statementofresponsibilityB.N. Honen, D.A. Saint, D.R. Laver
dc.identifier.citationJournal of Membrane Biology, 2003; 196(2):95-103
dc.identifier.doi10.1007/s00232-003-0628-9
dc.identifier.issn0022-2631
dc.identifier.issn1432-1424
dc.identifier.urihttp://hdl.handle.net/2440/3059
dc.language.isoen
dc.publisherSpringer-Verlag
dc.source.urihttp://www.springerlink.com/content/ddnybbl31bktn898/?p=3281f1d1b52a4e598042fe2b28962301&pi=3
dc.subjectIon channels/membrane transport
dc.subjectCalcium cycling/excitation-contraction coupling
dc.subjectArtificial lipid bilayers
dc.subjectContractile function
dc.subjectCalcium release channels
dc.titleSuppression of calcium sparks in rat ventricular myocytes and direct inhibition of sheep cardiac RyR channels by EPA, DHA and oleic acid
dc.typeJournal article
pubs.publication-statusPublished

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