阿魏酸钠对家兔心室肌细胞钾通道电流的影响  

Effects of sodium ferulate on potassium channel currents in isolated rabbit ventricular myocytes

作　　者：周彤[1,2] 毛晓波[1] 毛奕[1] 柳强妮[3] 曾秋棠[1] 

机构地区：[1]华中科技大学协和医院心内科华中科技大学心血管病研究所,武汉430022 [2]内蒙古医学附第三附属医院心内科,内蒙古包头014010 [3]华中科技大学同济医学院药理系

出　　处：《临床心血管病杂志》2009年第8期588-592,共5页Journal of Clinical Cardiology

基　　金：湖北省重大科技攻关项目(No:2006AA301A04)

摘　　要：目的:探讨阿魏酸钠对家兔心室肌细胞膜延迟整流钾电流快速与缓慢激活成分(IKr、IKs)、内向整流钾电流(IK1)、瞬时外向钾电流(Ito)的影响。方法:酶解法分离单个家兔心室肌细胞,以经典的Ⅲ类药胺碘酮为对照,采用全细胞膜片钳技术记录浓度为3.0、10.0、30.0、100.0μmol/L的阿魏酸钠对IKr、IKs、IK1、Ito的作用。结果:阿魏酸钠的作用弱于胺碘酮,二者均可浓度依赖性抑制IKr、IKs时间依赖性外向电流及尾电流(IKr,tail、IKs,tail)。不同浓度的阿魏酸钠对IKr,tail的抑制率为:(12.1±2.5)%、(24.1±3.0)%、(47.0±5.8)%及(58.5±8.3)%(n=5,P<0.05);对IKs,tail的抑制率为:(15.6±6.4)%、(27.1±6.5)%、(45.6±5.8)%及(51.8±6.6)%(n=5,P<0.05),其对IKr,tail及IKs,tail的半数抑制浓度(IC50)均大于胺碘酮(43.6∶3.48μmol/L,44.9∶5.11μmol/L)。30.0、100.0μmol/L阿魏酸钠及10.0、30.0μmol/L胺碘酮可使IK1的I-V曲线左移,在-100mV及-20mV测试电压下,阿魏酸钠对IK1内向、外向电流抑制率小于胺碘酮(n=5,P<0.05)。阿魏酸钠与胺碘酮均不影响Ito及其I-V曲线。结论:阿魏酸钠复合阻滞复极期多种钾电流,可能是其抗心律失常作用的电生理机制之一。Objective：To study the effect of sodium ferulate on rapidly and slowly activating component of delayed rectifier potassium current （Ikr, Iks）, inwardly rectified potassium current （Ik1） and transient outward potassium current （Ito） in isolated rabbit ventricular myocytes. Method：Compared with amiodarone-a typical class Ⅲ antiarrhythmic drug, single rabbits ventricular myocytes were isolated enzymatically and whole ceil patch clamp recording technique was used to record the changes of Ikr, Iks, Ik1 and Ito following the administration of sodium ferulate at 3.0, 10.0, 30.0 and 100.0umol/L. Result：Sodium ferulate was inferior to amiodarone, though both of them could block the time-dependent outward current and tail current of Ikr and Iks which had concentration dependence. Peak tail current of Ikr were reduced 12. 1%±2.5%, 24.1%±3.0%, 47.0 % ± 5.8% and 58.5% ＋ 8.3% （n=5, P〈0.05）, while, Peak tail current of Iks were reduced 15.6%±6.4%, 27.1%＋6.5%, 45.6%＋ 5.8 % and 51.8%±6.6% （n = 5, P〈0.05） respectively. IC50 （ the concentration for half-maximal block） were higher than amiodarone （43.6 vs 3.48 umol/L, 44.9 vs 5.11 umol/L）. At test potential of -100 mV and -20 mV, Ik1 was significantly decreased in amiodarone than in sodium ferulate （n=5, P〈0.05）. The current-voltage curve of IK1 moved left by sodium ferulate （30.0, 100.0 umol/L） or amiodarone （10.0, 30.0umol/L）. However, neither of them alter Ito and it＇s current-voltage curve. Conclusion：Sodium ferulate could block potassium channels, these may be the related mechanisms of its antiarrhythmic effects.

关 键 词：心律失常 阿魏酸钠 膜片钳术 钾通道(Ikr、Iks、 Ix1、Ito) 肌细胞 心脏 

分 类 号：R541.7[医药卫生—心血管疾病]