蝙蝠葛碱对豚鼠心室肌细胞钾电流的抑制作用。

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

作者信息

Xia J S, Guo D L, Zhang Y, Zhou Z N, Zeng F D, Hu C J

机构信息

Department of Clinical Pharmacology, Tongji Medical University, Wuhan 430030, China.

出版信息

Acta Pharmacol Sin. 2000 Jan;21(1):60-4.

PMID:11263249

Abstract

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 mumol.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) mumol.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 mumol.L-1 (n = 6 cells from 3 animals, P > 0.05). (2) Dau 1-100 mumol.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) mumol.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 mumol.L-1 (n = 8 cells from 4 animals, P > 0.05). (3) Addition of Dau 30 mumol.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 depolarizations. (4) Dau 20 mumol.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.

摘要

目的

研究蝙蝠葛碱（Dau）对豚鼠心室肌细胞延迟整流钾电流的快速激活成分（IKr）、缓慢激活成分（IKs）以及内向整流钾电流（IKl）的影响。

方法

采用酶解法分离单个心肌细胞。运用膜片钳技术的全细胞模式记录电流。

结果

（1）1、3、10、30和100μmol·L-1的Dau以浓度依赖方式阻断IKr和尾电流（IKr-tail）。阻断IKr-tail的IC50为16（95%可信区间：13 - 22）μmol·L-1。IKr-tail失活的时间常数在对照组为（140±38）ms，在30μmol·L-1的Dau存在时为（130±26）ms（n = 6个细胞，来自3只动物，P>0.05）。（2）1 - 100μmol·L-1的Dau对IKs和尾电流（IKs-tail）产生浓度依赖性阻断。阻断IKs-tail的IC50值为33（95%可信区间：24 - 46）μmol·L-1。IKs-tail失活的时间常数在对照组为（92±18）ms，在30μmol·L-1的Dau存在时为（84±16）ms（n = 8个细胞，来自4只动物，P>0.05）。（3）加入30μmol·L-1的Dau诱导IKs和IKs-tail阻断（n = 7个细胞，来自3只动物）。IKs和IKs-tail的阻断程度取决于测试电位，随着去极化程度越正而增加。（4）20μmol·L-1的Dau主要阻断IKl的内向成分，并使反转电位从-72mV（对照组）降至-78mV（n = 6个细胞，来自3只动物）。