Protein kinase A is activated by the n-3 polyunsaturated fatty acid eicosapentaenoic acid in rat ventricular muscle

N. Szentandrássy, M. R. Pérez-Bido, E. Alonzo, N. Negretti, Stephen C. O'neill

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

During cardiac ischaemia antiarrhythmic n-3 polyunsaturated fatty acids (PUFAs) are released following activation of phospholipase A2, if they are in the diet prior to ischaemia. Here we show a positive lusitropic effect of one such PUFA, eicosapentaenoic acid (EPA) in the antiarrhythmic concentration range in Langendorff hearts and isolated rat ventricular myocytes due to activation of protein kinase A (PKA). Several different approaches indicated activation of PKA by EPA (5-10 μmol l-1): the time constant of decay of the systolic Ca2+ transient decreased to 65.3 ± 5.0% of control, Western blot analysis showed a fourfold increase in phospholamban phosphorylation, and PKA activity increased by 21.0 ± 7.3%. In addition myofilament Ca2+ sensitivity was reduced in EPA; this too may have resulted from PKA activation. We also found that EPA inhibited L-type Ca2+ current by 38.7 ± 3.9% but this increased to 63.3 ± 3.4% in 10 μmol l-1 H89 (to inhibit PKA), providing further evidence of activation of PKA by EPA. PKA inhibition also prevented the lusitropic effect of EPA on the systolic Ca2+ transient and contraction. Our measurements show, however, PKA activation in EPA cannot be explained by increased cAMP levels and alternative mechanisms for PKA activation are discussed. The combined lusitropic effect and inhibition of contraction by EPA may, respectively, combat diastolic dysfunction in ischaemic cardiac muscle and promote cell survival by preserving ATP. This is a further level of protection for the heart in addition to the well-documented antiarrhythmic qualities of these fatty acids.

Original languageEnglish
Pages (from-to)349-358
Number of pages10
JournalJournal of Physiology
Volume582
Issue number1
DOIs
Publication statusPublished - Jul 1 2007

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Eicosapentaenoic Acid
Omega-3 Fatty Acids
Cyclic AMP-Dependent Protein Kinases
Muscles
Ischemia
Myofibrils
Phospholipases A2
Unsaturated Fatty Acids
Cardiac Myocytes
Muscle Cells
Cell Survival
Fatty Acids
Adenosine Triphosphate
Western Blotting
Phosphorylation
Diet

ASJC Scopus subject areas

  • Physiology

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Protein kinase A is activated by the n-3 polyunsaturated fatty acid eicosapentaenoic acid in rat ventricular muscle. / Szentandrássy, N.; Pérez-Bido, M. R.; Alonzo, E.; Negretti, N.; O'neill, Stephen C.

In: Journal of Physiology, Vol. 582, No. 1, 01.07.2007, p. 349-358.

Research output: Contribution to journalArticle

Szentandrássy, N. ; Pérez-Bido, M. R. ; Alonzo, E. ; Negretti, N. ; O'neill, Stephen C. / Protein kinase A is activated by the n-3 polyunsaturated fatty acid eicosapentaenoic acid in rat ventricular muscle. In: Journal of Physiology. 2007 ; Vol. 582, No. 1. pp. 349-358.
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