Inhibitory effects of dauricine on potassium currents in guinea pig ventricular myocytes^1  

蝙蝠葛碱对豚鼠心室肌细胞钾电流的阻断作用(英文)

作　　者：夏敬生[1] 郭东林[1] 张翼[2] 周兆年[2] 曾繁典[1] 胡崇家[1] 

机构地区：[1]同济医科大学临床药理研究所 [2]中国科学院上海生理研究所

出　　处：《Acta Pharmacologica Sinica》2000年第1期62-66,共5页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China. No 39670834.

摘　　要：AIM: To study the effects of dauricine(Dau) on the rapidly activating component (Ikr), the slowly activating component (Iks) of the delayed rectifier potassium current, and the inward rectifier potassium current (Ikl) in guinea pig ventricular myocytes. METHODS: Single myocytes were dissociated by enzymatic dissociation method. The currents were recorded with the whole-cell configuration of the patch-clamp technique. RESULTS: (1) Dau 1, 3, 10, 30, and 100 μmol·L-1 blocked IKr and tail current (IKr-tail)in a concentration-dependent manner. The IC50 for block of IKr-tail was 16 (95 % confidence limits: 13-22) μmol·L-1. The time constant of IKr-tail deactivation was (140±38) ms in the control and (130±26) ms in the presence of Dau 30 μmol·L-1 ( n =6 cells from 3 animals, P > 0.05). (2) Dau 1 - 100 μmol·L-1 produced concentration-dependent blocks of Iks and tail current ( Iks-tail). The IC50 value for block of IKs-tail was 33 (95 % confidence limits: 24-46) μmol·L-1. The time constant of Iks-tail deactivation was (92±18) ms in the control and (84±16) ms in the presence of Dau 30 /μmol·L-1 ( n =8 cells from 4 animals, P > 0.05). (3) Addition of Dau 30 μmol·L-1 induced block of IkS and Iks-tail(n= 7 cells from 3 animals). The degree of block of IKs and Iks-tail depended on test potentials, increasing with more positive depolariza- tions. (4) Dau 20μmol·L-1 blocked mainly inward component of Ikl and reduced the reversal potential from - 72 mV (control) to - 78 mV (n = 6 cells from 3 animals). CONCLUSION: (1) Dau inhibited Iks, but not the process of Iks deactivation. (2) Dau blocked Ikr, but not the process of deactivation. (3) Dau had a blocking effect on Ikl.目的:研究蝙蝠葛碱对豚鼠心室肌细胞快激活(I_(Kr))和慢激活(I_(Ks))延迟整流钾电流及内向整流钾电流(I_(K1))的作用。方法:酶解法制备单个心室肌细胞。电压箝制方式下全细胞记录豚鼠单个心室肌细胞钾通道电流。结果:蝙蝠葛碱1-100μmol·L^(-1)浓度依赖性阻断I_(Ks),I_(Ks-tail)[IC_(50)=33(95 ％可信限:24-46)μmol·L^(-1)]及I_(Kr),I_(Kr-tail)[IC_(50))=16 (95％可信限:13-22)μmol·L^(-1)]。对I_(Ks-tail),I_(Kr-tail)的去激活过程无明显影响,给药前的时间常数分别为(92±18)ms和(140±38)ms,给药后分别为(84±16)ms和(130±26)ms(P>0.05)。蝙蝠葛碱对I_(Ks)的抑制作用具有电压依赖性。 蝙蝠葛碱20μmol·L^(-1)对I_(K1)的内向部分具有阻断作用。结论:蝙蝠葛碱对I_(Kr)和I_(Ks)具有阻断作用,但不影响此两种成分的去激活过程. 蝙蝠葛碱同时具有阻断I_(K1)的作用。

关 键 词：DAURICINE MYOCARDIUM potassium channels patch-clamp techniques 

分 类 号：R285[医药卫生—中药学]