CAJ | 학술논문

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.
본연구시재성년설초적심기상연구다불포화지방산(PUFA)대전압문공갑통도적효응.아문관찰도, n-3 PUFA능억제단시성외향갑전류(I to)화연지정류갑전류(I K),이대내향정류갑전류(I K1)칙몰유명현영향.이십이탄륙희산(DHA)대I to화I k능산생농도의뢰성적억제작용,기IC50분별위7.5 화20 μmol/L, 단불영향I K1.이십탄오희산(EPA)대저삼충갑통도적작용여DHA 상사.화생사희산(5 혹10 μmol/L)선인기IK적억제,연후인기IK,AA적격활;용배양합매억제제소염통가이조단화생사희산격활IK,AA적작용.불구유항심률실상작용적단불포화지방산화포화지방산도불명현영향저사갑통도적활성.상술실험결과증명,n-3 PUFA능억제심기세포적Ito화IK, 단화아문이전보도적PUFA대심기납전류화개전류적작용상비,기대I to화I k억제작용적효능교저.n-3 PUFA적항심률실상효응가능여타문억제심기납、개、갑통도적작용유관.
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.