苄普地尔对豚鼠甲亢性肥厚心肌中延迟整流钾电流的抑制作用  

BEPRIDIL INHIBITION ON THE DELAYED RECTIFIER K^+ CURRENTS IN THYROXINE INDUCED HYPERTROPHIED GUINEA PIG VENTRICULAR MYOCYTES

作　　者：张广钦[1] 郝雪梅[2] 马玉萍[1] 周培爱[2] 吴才宏[2] 戴德哉[1] 

机构地区：[1]中国药科大学药理研究室,江苏南京210009 [2]北京大学生物膜与膜生物工程国家重点实验室,北京100871

出　　处：《药学学报》2001年第7期489-492,共4页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目 (3 9870 883 )

摘　　要：目的　研究苄普地尔 (bepridil)对肥厚心肌细胞延迟整流钾电流 (IK)中快激活成份 (IKr)和慢激活成份(IKs)及内向整流钾电流 (IK1 )的作用。方法　全细胞膜片钳技术。结果　在肥厚心肌细胞中 ,Bepridil 30 μmol·L- 1 对IKr及IKs有阻断作用 ,抑制率分别为 2 0 9% (0mV)和 2 7 2 % (+5 0mV)。“Envelopeoftail”显示bepridil对IKs的阻断作用大于IKr。Bepridil(1- 10 0 μmol·L- 1 )浓度依赖性的阻断IKs及IKr,其IC5 0 分别为 2 3 8μmol·L- 1 和 46 7μmol·L- 1 。Bepridil30 μmol·L- 1 也能阻断IK1 ,抑制率为 15 1% (- 10 0mV) ,但不影响其反转电位。结论　Bepridil对甲亢性豚鼠肥厚心肌中IKs,IKr及IK1AIM To study the effects of bepridil on the rapidly activating component ( I Kr ), the slowly activating component ( I Ks ) of the delayed rectifier potassium current and the inward rectifier potassium current ( I K1 ) in hypertrophied guinea pig ventricular myocytes. METHODS The whole cell patch clamp techniques were used. RESULTS In hypertrophied guinea pig ventricular myocytes, bepridil 30 μmol·L -1 markedly inhibited I Kr and I Ks (by 20 9% and 27 2% at 0 mV and +50 mV, respectively). The effect of bepridil on I Ks was larger than on I Kr . Bepridil 30 μmol·L -1 also significantly inhibited the inward component of I K1 (by 15 1% at +100 mV), but the reverse potential of I K1 was unaffected. Bepridil (1-100 μmol·L -1 ) was shown to inhibit I Kr and I Ks in a concentration dependent manner. Their IC 50 were 46 7 μmol·L -1 and 23 8 μmol·L -1 , respectively. CONCLUSION Bepridil inhibit I Kr , I Ks and I K1 in hypertrophied guinea pig ventricular myocytes, which may be important in understanding the antiarrhythmic effects of this drug.

关 键 词：苄普地尔 甲状腺素 甲亢性肥厚心肌细胞 钾通道 膜片钳技术 豚鼠 

分 类 号：R541.85[医药卫生—心血管疾病] R972.2[医药卫生—内科学]