甲基苯丙胺对豚鼠心室肌细胞动作电位及延迟整流钾电流的影响(英文)  

Effect of methylamphetamine on action potential and delayed rectifier potassium current in guinea-pig ventricular myocytes

作　　者：周延明[1] 梁若冰[1,2] 赵秀丽[3] 张明辉[3] 武峰[3] 朱波[1] 

机构地区：[1]黑龙江省公安厅安康医院内科,黑龙江哈尔滨150078 [2]黑龙江大学研究生院,黑龙江哈尔滨150080 [3]首都医科大学附属北京同仁医院临床药理科,北京100730

出　　处：《中国药理学与毒理学杂志》2010年第6期449-454,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：The project supported by the Key Technological Project of Heilongjiang Province (GB07C32408)~~

摘　　要：目的研究甲基苯丙胺对心血管系统的毒性作用及其机制。方法分离豚鼠心室肌细胞,采用全细胞膜片钳技术获取并分析心室肌细胞延迟整流钾电流(IK)及动作电位(AP)水平。结果甲基苯丙胺0.5mmol·L-1使豚鼠心室肌细胞AP幅值从121.6mV降至106.0mV,能延长动作电位时程(APD),但不改变静息电位水平。其中动作电位复极10%,25%,50%,75%及90%时程(APD10,APD25,APD50,APD75,APD90)分别延长179.0%,88.7%,47.7%,43.4%和31.9%(P<0.05)。甲基苯丙胺0.5mmol·L-1使快速激活延迟整流钾电流(IKr)和缓慢激活延迟整流钾电流(IKs)的膜电位水平降低,电流-电压曲线下移,但曲线形状不变,冲洗后能部分恢复。用含甲基苯丙胺0.01,0.1,0.5,1.0和3.0mmol·L-1的细胞外液分别灌流细胞5min,甲基苯丙胺对IKr尾电流幅度呈浓度依赖性的阻断作用,冲洗后能部分恢复。甲基苯丙胺对IKs尾电流的影响也非常显著(P<0.05)。结论甲基苯丙胺对豚鼠心室肌细胞的IK及AP都有不同程度的影响,这可能是甲基苯丙胺造成心脏损伤的电生理机制之一。OBJECTIVE To explore the mechanism of methylamphetamine(MA) on heart toxicity.METHODSThe effects of MA on delayed rectifier potassium current(IK) and action potential(AP) were analyzed in isolated guinea-pig ventricular myocytes by the whole-cell patch clamp technique.RESULTS MA 0.5 mmol·L-1 decreased AP from 121.6 to 106.0 mV and delayed the action potential duration(APD),but had no effect on the resting potential.The 10%,25%,50%,75% and 90% of APD(APD10,APD25,APD50,APD75 and APD90) were delayed by 179.0%,88.7%,47.7%,43.4% and 31.9%,respectively(P<0.05).MA 0.5 mmol·L-1 inhibited the membrane potential of rapidly activating delayed rectifier potassium current(IKr) and slowly activating delayed rectifier potassium current(IKs),downward shifted the Ⅰ-Ⅴ curve,but had no effect on the curve shape and could be partly recovered after flushing.The tail current IKr was blocked concentration-dependently after perfused by MA 0.01-3.0 mmol·L-1 for 5 min,and could be partly recovered after flushing.IKs tail current was similarly inhibited by MA.CONCLUSION MA has inhibitory effects on IK and AP in ventricular myocytes,which may be one of the possible electrophysiological mechanisms of the cardiac damage caused by MA.

关 键 词：甲基苯丙胺 肌细胞 心脏 动作电位 延迟整流钾通道 

分 类 号：R965[医药卫生—药理学]