摘要
目的:研究替米沙坦对表达在卵母细胞上的克隆人类Kv1.5通道的作用,探讨其在心脏复极中的潜在效应。方法:在非洲爪蟾卵母细胞上异源表达克隆人类Kv1.5通道基因,使用双电极电压钳技术记录全细胞电流,检测药物对Ikur电流的影响。结果:替米沙坦以电压依赖性和浓度依赖性方式抑制Kv1.5通道电流,且对峰电流及1.5s末端电流的抑制效应不同,在1μmol/L浓度下,抑制效应分别达到(7.75±2.39)和(52.64±3.77),其半抑制浓度(IC50)分别为(2.25±0.97)μmol/L和(0.82±0.39)μmol/L。替米沙坦对通道的稳态失活没有显著改变,在对照条件下,V1/2的值为(14.47±3.71)mV,斜坡因子k为(23.24±3.86)mV;在1μmol/L替米沙坦作用下,V1/2和k的值分别为(14.38±4.62)mV和(26.26±5.04)mV(n=6,P>0.05)。同时,替米沙坦显著加速了Kv1.5通道的失活。在对照条件下,Kv1.5通道的失活慢时间常数是(693.74±23.16)ms,在应用1μmol/L替米沙坦后,其失活的慢时间常数下降为(523.85±10.28)ms(n=5,P<0.05)。结论:替米沙坦在临床有效浓度范围内能显著抑制表达在卵母细胞上的Ikur电流,提示它兼有选择性阻滞Kv1.5通道的作用。
Objective：To uncover the potential effects of telmisartan （an AT1 receptor blocker） in cardiac repolarization, by investigating the pharmacological effect of telmisartan on cloned human Kvl. 5 potassium channel expressed in Xenopus ooeytes. Method：Kvl. 5 cRNA channel gene was expressed in xenopus oocytes and channel current was recorded using standard two-microeleetrode voltage clamp techniques in control condition or telmisartan intervention. Result： Telmisartan inhibited Kv1. 5 channel in a concentration-and voltage-dependent manner, and the efficacy of blockade was different at peak and 1.5s end pulse currents, which was （21.48±2.40）% and（ 95.67±9.09） % at the absence and presence of 1umol telmisartan, respectively. The IC50 is （2.25±1.14）umol and （0.82zk0.43）bLmol, respectively. The steady-state inactivation of Kv1. 5 is not significant altered, the V1/2 and slope factor were （14.47±3.71）mV （control） vs （14.38±4.62） mV and （23.24±3.86） mV （control） vs （26.26 ± 5.04） mV（n =6, P〉0.05） at the absence and presence of telmisartan, respectively. Meanwhile, telmisarran remarkably accelerated inactivation of the channel. In control condition, the slow time constant of inactiva tion was （693.74±23.16） ms, however, at 1 uM telmisartan, the slow time constant was （523.85±10.28） ms （n= 5, P〈0.05）. Conclusion..Telmisartan significantly inhibits Ikur currents expressed in Xenopus occytes at clinical therapeutic concentration, which indicates its＇ combining selective Kvl. 5 channel blockade effect.
出处
《临床心血管病杂志》
CAS
CSCD
北大核心
2008年第11期859-863,共5页
Journal of Clinical Cardiology
基金
国家自然科学基金项目(No:30470711)
