Received 2002-02-27 Accepted 2002-03-15

This study was supported in part by research grants 9930254N (Y.F.X.) from the American Heart Association, and DK38165 & HL62284 (A.L.) and DA12762 (J.P.M) from the National Health Institute of the U.S. Public Health Service.

*Corresponding author. Phone: (617)667-8649; Fax: (617)667-4833;

Email: yxiao@caregroup.harvard.edu

Acta Physiologica Sinica Aug. 2002, 54 (4), 271~281

Research Paper

Effects of polyunsaturated fatty acids on cardiac voltage-activated K+ currents in adult ferret cardiomyocytes

Yong-Fu XIAO1,2,*, James P. MORGAN1, Alexander LEAF 2

1Stem Cell Research Laboratory, Beth Israel Deaconess Medical Center;

2Massachusetts General Hospital; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA

Abstract: This study was carried out in adult ferret cardiomyocytes to investigate the effects of the n-3 polyunsaturated fatty acids (PUFAs) on voltage-gated K+ currents. We report that the two outward K+ currents: the transient outward K+ current (Ito) and the delayed rectifier K+ current (IK), are both inhibited by the n-3 PUFAs, while the inwardly rectifying K+ current (IK1) is unaffected by the n-3 PUFAs. Docosahexaenoic acid (C22:6n-3, DHA) produced a concentration-dependent suppression of Ito and IK in adult ferret cardiomyocytes with an IC50 of 7.5 and 20 µmol/L, respectively; but not IK1. In addition, eicosapentaenoic acid (C20:5n-3, EPA) had the effects on the three K+ channels similar to DHA. Arachidonic acid (C20:4n-6, AA) at 5 or 10 µmol/L, after an initial inhibitory effect on IK, caused an activation of IK,AA which was prevented by pretreatment with indomethacin, a cyclooxygenase inhibitor. Monounsaturated and saturated fatty acids, which are not antiarrhythmic, lack the effects on these K+ currents. Our results demonstrate that the n-3 PUFAs inhibit cardiac Ito and IK with much less potency compared to their effects on cardiac Na+ and Ca2+ currents as we reported previously. This inhibition of the cardiac ion currents by the n-3 PUFAs may contribute to their antiarrhythmic actions.

Key words: cardiomyocytes; potassium channels; arrhythmia; polyunsaturated fatty acids

多不饱和脂肪酸对成年雪貂心肌钾通道的作用

萧永福1,2,*, James P. MORGAN1, Alexander LEAF2

1哈佛医学院医学系贝斯以色列迪肯尼斯医学中心干细胞实验室; 2麻省总医院, 美国波士顿

摘 要: 本研究是在成年雪貂的心肌上研究多不饱和脂肪酸(PUFA)对电压门控钾通道的效应。我们观察到, n-3 PUFA能抑制短时性外向钾电流(Ito)和延迟整流钾电流(IK), 而对内向整流钾电流(IK1)则没有明显影响。二十二碳六烯酸(DHA)对I to和I k能产生浓度依赖性的抑制作用, 其IC50分别为7.5 和20 µmol/L, 但不影响I K1。二十碳五烯酸(EPA)对这三种钾通道的作用与DHA 相似。花生四烯酸(5 或10 µmol/L)先引起IK的抑制, 然后引起IK,AA的激活;用环氧合酶抑制剂消炎痛可以阻断花生四烯酸激活IK,AA的作用。不具有抗心律失常作用的单不饱和脂肪酸和饱和脂肪酸都不明显影响这些钾通道的活性。上述实验结果证明, n-3 PUFA能抑制心肌细胞的Ito和IK, 但和我们以前报道的PUFA对心肌钠电流和钙电流的作用相比, 其对I to和I k抑制作用的效能较低。n-3 PUFA的抗心律失常效应可能与它们抑制心肌钠、 钙、 钾通道的作用有关。

关键词: 心肌细胞; 钾通道; 心律失常; 多不饱和脂肪酸

学科分类号: Q463; Q689