Influence of phospholipid long chain polyunsaturated fatty acid composition on neonatal rat cardiomyocyte function in physiological conditions and during glucose-free hypoxia-reoxygenation

• Published in: Molecular and cellular biochemistry 1997-10, Vol.175 (1-2), p.253-262
• Main Authors: Durot, I, Athias, P, Oudot, F, Grynberg, A
• Format: Article
• Language: English
• Subjects: Action Potentials; Animals; Animals, Newborn; Arachidonic Acids - pharmacology; Biochemistry, Molecular Biology; Cardiovascular diseases; Cell Hypoxia; Cells, Cultured; Chromatography, Gas; Diet; Docosahexaenoic Acids - pharmacology; Eicosapentaenoic Acid - pharmacology; Electrophysiology; Fatty acids; Fatty Acids, Unsaturated - pharmacology; Glucose - metabolism; Hypoxia; Life Sciences; Muscular system; Myocardial Contraction; Myocardium - cytology; Myocardium - metabolism; Oxygen Consumption; Physiology; Polyunsaturated fatty acids; Rats; Rats, Wistar; Ventricular Function - drug effects
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1023/A:1006817901323

There is evidence that dietary polyunsaturated fatty acids (PUFA) may protect against cardiovascular diseases, but the involvement of the cardiac muscle cell in this beneficial action remain largely unknown. The present study compared the respective influence of n-3 and n-6 PUFA on the function of cultured neonatal rat cardiomyocytes (CM). Cells were grown for 4 days in media enriched either n-3 (eicosapentaenoic acid, EPA and docosahexaenoic acid, DHA) or n-6 (arachidonic acid, AA) PUFA. The PUFA n-6/n-3 ratio in the phospholipids was close to 1 and 20 in the n-3 and n-6 cells, respectively. The transmembrane potentials were recorded using microelectrodes and the contractions were monitored with a photoelectric device. In physiological conditions, the increase of n-6 PUFA level in the phospholipids resulted in a significant decrease in the maximal rate of initial depolarization (-16%). In opposition, the action potential amplitude and duration were not altered, and the cell contraction outline was not affected. Ischemia was simulated in vitro using a substrate-free, hypoxia-reoxygenation procedure in a specially designed gas-flow chamber. The progressive loss of electrical activity induced by the substrate-free, hypoxic treatment was affected by the n-6/n-3 ratio, since the n-6 rich CM displayed a slower depression of the AP amplitude and duration parameters. Conversely, the recovery of the resting potential (MDP) during reoxygenation was faster in n-3 CM, whereas the recovery of the contraction parameters was unaffected by the fatty acid composition of the cells. These results suggested that, in physiological conditions, the modification of long chain PUFA balance in the phospholipids of cardiac muscle cells may modulate the initial AP upstroke, which is governed by sodium channels. Moreover, the presence of n-3 PUFA appeared to accelerate the electrical depression during substrate-free hypoxia but in turn to allow a faster recovery upon reoxygenation.