盐酸非洛普对豚鼠心室肌细胞延迟整流钾电流的抑制作用  

Inhibitory effects of phenoprolamine hydrochloride on delayed rectifier potassium currents in ventricular myocytes of guinea pig

作　　者：胡晓东[1] 钱家庆[2] 

机构地区：[1]中山大学中山医学院生理学教研室,广东广州510080 [2]华中科技大学同济医学院药理学教研室,湖北武汉430030

出　　处：《中国药理学与毒理学杂志》2002年第5期343-347,共5页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金资助项目 (38970 834)

摘　　要：目的　已知盐酸非洛普〔1 (2 ,6 二甲基苯氧基 ) 2 (3,4 二甲氧基苯乙氨基 )丙烷盐酸盐 ,DDPH〕对心肌钙电流和钠电流具有抑制作用 ,为全面了解其抗心律失常作用的离子机理 ,研究其对延迟整流钾电流的影响。方法　全细胞膜片钳技术记录豚鼠心室肌细胞快激活的延迟整流钾电流的尾电流(IKr tail)和慢激活的延迟整流钾电流 (IKs)及其尾电流 (IKs tail)。结果　DDPH(1～ 10 0 μmol·L- 1)浓度依赖性地抑制IKr tail,其IC50 为 7.0 (95 %可信限为4 .2 3～ 9.76 ) μmol·L- 1;DDPH 10 μmol·L- 1对IKr tail具有电压依赖性抑制作用。DDPH 10 ,30和 10 0 μmol·L- 1可浓度依赖性地抑制IKs及其IKs tail,使IKs从给药前的 (9.1± 0 .7)pA·pF- 1分别降至 (7.7± 1.7) ,(7.5± 1.8)和 (5 .6± 1.8)pA·pF- 1(P <0 .0 1) ;使IKs tail从给药前的 (1.4± 0 .2 )pA·pF- 1分别降至(1.1± 0 .2 ) ,(0 .9± 0 .2 )和 (0 .6± 0 .2 )pA·pF- 1(P <0 .0 5或P <0 .0 1) ;DDPH 30 μmol·L- 1对IKs tail具有电压依赖性抑制作用。结论　DDPH对豚鼠心室肌细胞延迟整钾电流具有抑制作用。AIM On the basis of the inhibitory effects of phenoprolamine hydrochloride 〔1 (2,6 dimethylphenoxy) 2 (3,4 dimethoxyphenylethy lamino) propane hydrochloride , DDPH〕 on the calcium current and sodium current, its effects on rapidly activated component (I Kr ) and slowly activated component (I Ks ) of delayed rectifier potassium current were studied in single ventricular myocyte of guinea pig for fully understanding the ionic mechanism of its antiarrhythmic effect. METHODS Whole cell patch clamp technique was used to record the tail currents of I Kr (I Kr tail ) and I Ks (I Ks tail ). RESULTS DDPH (1-100 μmol·L -1 ) dose dependently inhibited the I Kr tail with an IC 50 value of 7.0(95% confidence limit:4.23-9.76)μmol·L -1 . DDPH 10 μmol·L -1 blocked I Kr tail in a voltage dependent manner. After exposure to DDPH 10, 30 and 100 μmol·L -1 , I Ks decreased from (9.1±0.7)pA·pF -1 to (7.7±1.7),(7.5±1.8) and (5.6±1.8)pA·pF -1 , respectively; and the I Ks tail from (1.4±0.2)pA·pF -1 to (1.1±0.2),(0.9±0.2) and (0.6±0.2)pA·pF -1 , respectively. DDPH 30 μmol·L -1 inhibited I Ks tail voltage dependently. CONCLUSION DDPH has inhibitory effects on I Kr and I Ks .

关 键 词：盐酸非洛普 心室肌细胞 延迟整流钾电流 抑制作用 心律失常 钾通道 膜片钳技术 

分 类 号：R965[医药卫生—药理学]