Durot I, Athias P, Oudot F, Grynberg A
Laboratoire de Physiopathologie et Pharmacologie Cardiovasculaires Experimentales, Faculté de Médecine, Dijon, France.
Mol Cell Biochem. 1997 Oct;175(1-2):253-62. 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.
有证据表明，膳食多不饱和脂肪酸（PUFA）可能预防心血管疾病，但心肌细胞在这一有益作用中的参与情况仍 largely 未知。本研究比较了 n-3 和 n-6 PUFA 对培养的新生大鼠心肌细胞（CM）功能的各自影响。细胞在富含 n-3（二十碳五烯酸，EPA 和二十二碳六烯酸，DHA）或 n-6（花生四烯酸，AA）PUFA 的培养基中培养 4 天。n-3 和 n-6 细胞中磷脂的 PUFA n-6/n-3 比值分别接近 1 和 20。使用微电极记录跨膜电位，并用光电装置监测收缩情况。在生理条件下，磷脂中 n-6 PUFA 水平的增加导致初始去极化最大速率显著降低（-16%）。相反，动作电位幅度和持续时间未改变，细胞收缩轮廓也未受影响。在一个专门设计的气流室中，使用无底物、缺氧复氧程序在体外模拟缺血。无底物、缺氧处理引起的电活动逐渐丧失受 n-6/n-3 比值影响，因为富含 n-6 的 CM 显示出 AP 幅度和持续时间参数的下降较慢。相反，复氧期间静息电位（MDP）的恢复在 n-3 CM 中更快，而收缩参数的恢复不受细胞脂肪酸组成的影响。这些结果表明，在生理条件下，心肌细胞磷脂中长链 PUFA 平衡的改变可能调节由钠通道控制的初始 AP 上升支。此外，n-3 PUFA 的存在似乎加速了无底物缺氧期间的电抑制，但反过来又允许复氧时更快恢复。
