Li Gui-Rong, Sun Hai-Ying, Zhang Xiao-Hua, Cheng Lik-Cheung, Chiu Shui-Wah, Tse Hung-Fat, Lau Chu-Pak
Department of Medicine and Research Centre of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, SAR, China.
Cardiovasc Res. 2009 Feb 1;81(2):286-93. doi: 10.1093/cvr/cvn322. Epub 2008 Nov 24.
The omega-3 (n-3) polyunsaturated fatty acids (omega-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil were recently reported to have an anti-atrial fibrillation effect in humans; however, the ionic mechanisms of this effect are not fully understood. The present study was designed to determine the effects of EPA and DHA on transient outward and ultra-rapid delayed rectifier potassium currents (I(to) and I(Kur)) and the voltage-gated sodium current (I(Na)) in human atrial myocytes.
A whole-cell patch voltage clamp technique was employed to record I(to) and I(Kur), and I(Na) in human atrial myocytes. It was found that EPA and DHA inhibited I(to) in a concentration-dependent manner (IC(50): 6.2 microM for EPA; 4.1 microM for DHA) and positively shifted voltage-dependent activation of the current. In addition, I(Kur) was suppressed by 1-50 microM EPA (IC(50): 17.5 microM) and DHA (IC(50): 4.3 microM). Moreover, EPA and DHA reduced I(Na) in human atrial myocytes in a concentration-dependent manner (IC(50): 10.8 microM for EPA; 41.2 microM for DHA) and negatively shifted the potential of I(Na) availability. The I(Na) block by EPA or DHA was use-independent.
The present study demonstrates for the first time that EPA and DHA inhibit human atrial I(to), I(Kur), and I(Na) in a concentration-dependent manner; these effects may contribute, at least in part, to the anti-atrial fibrillation of omega-3 PUFAs in humans.
最近有报道称，鱼油中的ω-3（n-3）多不饱和脂肪酸（ω-3 PUFAs）二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）对人类具有抗心房颤动作用；然而，这种作用的离子机制尚未完全阐明。本研究旨在确定EPA和DHA对人心房肌细胞瞬时外向钾电流和超快速延迟整流钾电流（I(to)和I(Kur)）以及电压门控钠电流（I(Na)）的影响。
采用全细胞膜片钳电压钳技术记录人心房肌细胞的I(to)、I(Kur)和I(Na)。发现EPA和DHA以浓度依赖性方式抑制I(to)（IC(50)：EPA为6.2μM；DHA为4.1μM），并使电流的电压依赖性激活正向移位。此外，1-50μM的EPA（IC(50)：17.5μM）和DHA（IC(50)：4.3μM）可抑制I(Kur)。而且，EPA和DHA以浓度依赖性方式降低人心房肌细胞的I(Na)（IC(50)：EPA为10.8μM；DHA为41.2μM），并使I(Na)可用性电位负向移位。EPA或DHA对I(Na)的阻断与使用无关。
本研究首次证明EPA和DHA以浓度依赖性方式抑制人心房I(to)、I(Kur)和I(Na)；这些作用可能至少部分有助于ω-3 PUFAs对人类的抗心房颤动作用。
