Membrane docosahexaenoic acid vs. eicosapentaenoic acid and the beating function of the cardiomyocyte and its regulation through the adrenergic receptors

The β‐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 cardiomyoxytes did not provoke electrical or contraction modifications, except for a slightly lower plateau phase (−2 mV). Conversely, the β‐adrenergic function was affected at several levels: (i) the receptor affinity for dihydroalprenolol tended to decrease (Kd) without alteration of the number of β‐binding sites (βmax); (ii) the isoproterenol‐induced (10−7 M and 10−6M) cAMP production was significantly decreased (−20%); and (iii) the positive chronotropic response to β‐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 perment 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 β‐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 α‐adrenergic system (chronotropic response, receptor density, affinity for prasozin, and inositide phosphate production) were influenced by the membrane DHA content.