Membrane docosahexaenoic acid vs. eicosapentaenoic acid and the beating function of the cardiomyocyte and its regulation through the adrenergic receptors.
The beta-adrenergic system in cardiac muscle cells is influenced by the n-3 polyunsaturated fatty acid (PUFA) content in cell membranes. This study deals with the specific effect of docosahexaenoic acid (DHA) as compared to other n-3 PUFA, without modification of the arachidonic acid content. Increasing the DHA content in the phospholipids of isolated cardiomyocytes did not provoke electrical or contraction modifications, except for a slightly lower plateau phase (-2 mV). Conversely, the beta-adrenergic function was affected at several levels: (i) the receptor affinity for dihydroalprenolol tended to decrease (Kd) without alteration of the number of beta-binding sites (beta max); (ii) the isoproterenol-induced (10(-7) M and 10(-6) M) cAMP production was significantly decreased (-20%); and (iii) the positive chronotropic response to beta-adrenergic stimulation (isoproterenol, 10(-7) M) was significantly enhanced (+80%). In order to further investigate the relationship between the decreased cAMP and the increased chronotropic response, the cells were treated with dibutyryl-cAMP, a permeant analogue of cAMP, which elicited a significantly higher chronotropic response in DHA-enriched cells than in EPA-enriched cells +50%). The increase in DHA content in cardiac cell membranes phospholipids may thus affect the beta-adrenergic system through an increase of cAMP efficiency. Although the membrane phosphatidylinositols were largely involved in the PUFA alterations, none of the parameters related to alpha-adrenergic system (chronotropic response, receptor density, affinity for prasozin, and inositide phosphate production) were influenced by the membrane DHA content.
Grynberg
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A
INRA, Unité de Nutrition Lipidique, Dijon, France.
Fournier
A
A
Sergiel
J P
JP
Athias
P
P
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry; D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000032:analysis / Q000737:chemistry*; D015118:Eicosapentaenoic Acid / Q000032:analysis / Q000737:chemistry*; D006352:Heart Ventricles / Q000166:cytology; D009200:Myocardial Contraction / Q000502:physiology*; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid