Polyunsaturated fatty acids in cultured cardiomyocytes: effect on physiology and beta-adrenoceptor function

Abstract

This study was carried out to investigate the influence of the membrane fatty acid composition on the basal electrical and contractile activities and the response to beta-adrenergic stimulation of rat cardiac muscle cells in culture. Cells were grown for 3 days in a conventional serum culture medium and then incubated for 24 h in synthetic media containing either n-6 or n-3 as the sole source of polyunsaturated fatty acids (PUFA). The n-6/n-3 ratio in the phospholipids was 0.9 in the n-3 cells and 13.1 in the n-6 cells compared with 6.3 in controls cells. Such modifications did not alter action potentials and the main parameters related to contraction, although shortening was slightly accelerated in the n-6 cells. On the other hand, the positive chronotropic effect induced by isoproterenol was more pronounced (P less than 0.01) in n-3 cells than in n-6 cells. In addition, isoproterenol caused a decrease in contraction duration and in shortening and relaxation time that was less pronounced in n-6 than in control cells (P less than 0.01, P less than 0.01 and P less than 0.05, respectively). These results suggest that the PUFA balance in the phospholipids may contribute to modulate the cardiac adrenergic receptor system but not the membrane properties related to electro-mechanical functions.

Sympathoadrenergic overactivity and lipid metabolism

“…The increase in the contraction rate was maintained at a constant level during the 30 minutes of stimulation, and the spontaneous contraction rhythm returned to the basal level within a few minutes after agonist withdrawal (data not shown). This enhanced response in n-3 PUFA-enriched cardiomyocytes has already been reported in vitro [10], and was recently more specifically related to the presence of docosahexaenoic acid in the membranes, which increases the efficacy of cAMP [23]. Biochemical analysis revealed that neither fatty acid supply nor adrenergic stimulation affected the gross cell parameters, such as the amount of protein, the total amount of lipid, total phospholipids, triglycerides, and cholesterol (data not shown).…”

“…Stimulation by isoproterenol was maintained for 30 minutes and was repeated every 12 hours over 48 hours. During each treatment, the contraction was continuously monitored with a video motion detector [10] to control the chronotropic response to isoproterenol stimulation. Two hours after the last treatment, the cells were rinsed and harvested, and the lipids were extracted [11].…”

Effects of oleic acid and its congeners, elaidic and stearic acids, on the structural properties of phosphatidylethanolamine membranes

“…In this context, it is of special interest to study the effects of FAs on membrane structure because of its further influence on membrane protein function. Several works support the involvement of the plasma membrane properties in the control of membrane protein activity and the cell physiology (1,(39)(40)(41). Moreover, altered levels of FFAs have been associated with pathological states (38).…”

Bioassay development: The implications of cardiac myocyte motility in vitro

“…Myocyte cell suspensions were prepared with a modified version of a previously described dissociation technique (Courtois et al, 1992). Four neonatal Sprague Dawley rats (age 1-3 d) were sacrificed and the hearts were removed under sterile conditions under a laminar flow hood.…”