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

Xiao Yongfu, Morgan James P, Leaf Alexander

Stem Cell Research Laboratory, Beth Israel Deaconess Medical Center；Massachusetts General Hospital

摘要

This stud 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~+ current: the transient outward K~+ current (I_(to)) and the delayed rectifier K~+ current (I_K), are both inhibited by the n-3 PUFAs, while the inwardly rectifying K~+ current (I_(K1)) is unaffected by the n-3 PUFAs. Docosahexaenoic acid (C22: 6n-3, DHA) produced a concentration-dependent suppression of I_(to) and I_K in adult ferret cardiomyocytes with an IC_(50) of 7.5 and 20 μmol/L, respectively; but not I_(K1). 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 I_K, caused an activation of I_(K,AA) which was prevented by pretreatment with indomethacin, a cyclooxygenase inhibitor. Monounsaturated and saturated fatty acids, which are not atiarrhythmic, lack the effects on these K~+ currents. Our results demonstrate that the n-3 PUFAs inhibit cardiac I_(to) and I_K with much less potency compared to their effects on cardiac Na~+ and Ca~(2+) currents as we reported previously. This inhibition of the cardiac ion currents by the n-3 PUFAs may contribute to their antiarrhythmic actions.

关键词： 心肌细胞; 钾通道; 心律失常; 多不饱和脂肪酸

多不饱和脂肪酸对成年雪貂心肌钾通道的作用

萧永福, Morgan James P, Leaf Alexander

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.美国；麻省总医院.美国

Abstract

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（I_(to)）和延迟整流钾电流（I_K），而对内向整流钾电流（I_(K1)）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IC_(50)分别为7.5和20μmol/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10μmol/L）先引起I_K的抑制，然后引起I_(K,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I_(K,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I_(to)和I_K，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。

Key words: Cardiomyocytes;Potassium channels;Arrhythmia;Polyunsaturated fatty acids

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引用本文：

Xiao Yongfu, Morgan James P, Leaf Alexander. Effects of polyunsaturated fatty acids on cardiac voltage-activated K~+ currents in adult ferret cardiomyocytes[J]. 生理学报 2002; 54 (4): .

萧永福, Morgan James P, Leaf Alexander. 多不饱和脂肪酸对成年雪貂心肌钾通道的作用. Acta Physiol Sin 2002; 54 (4): (in Chinese with English abstract).