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《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:

2013年第5期

页码:

512-518

栏目:

基础研究

出版日期:

2013-09-25

文章信息/Info

Title:

Effects of diltiazem on activation and inactivation kinetics of fKv1.4 channel currents expressed in Xenopus oocytes

作者:

张 冬¹; 陈 卉¹; 2; 巢升平¹; 王智泉¹; 任江华¹

(1.武汉大学中南医院心内科，湖北 武汉 430071；2.武汉市普爱医院心内科，湖北 武汉 430033)

Author(s):

ZHANG Dong¹;  CHEN Hui¹; 2;  CHAO Sheng-ping¹;  WANG Zhi-quan¹;  REN Jiang-hua¹

(1.Department of Cardiology, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei, China; 2.Deptment of Cardiology, Wuhan Puai Hospital, Wuhan 430033, Hubei, China)

关键词:

地尔硫卓; Kv1.4; 钾通道; 激活; 失活; 非洲爪蟾

Keywords:

diltiazem;  Kv1.4;  potassium channel;  inactivation;  activation;  Xenopus

分类号:

R329.25

DOI:

-

文献标识码:

A

摘要:

目的:研究地尔硫卓对异源表达在卵母细胞上的克隆fKv1.4钾通道电流的激活及失活动力学影响。方法： 在非洲爪蟾卵母细胞上异源表达雪貂心脏来源的去N端Kv1.4（fKv1.4ΔN）通道基因，采用双电极电压钳制技术记录电流、记录药物对fKv1.4ΔN通道电流的影响。结果： 地尔硫卓以频率依赖性、电压依赖性及浓度依赖性的方式抑制fKv1.4ΔN通道电流，其半抑制浓度（IC50）为(241.04±23.06) μmol/L(+50 mV)。对照条件下，fKv1.4ΔN通道电流失活的表现为单指数方程拟合，在应用地尔硫卓后，fKv1.4ΔN通道电流失活变为双指数方程拟合，即药物诱导的快速失活成分及较慢的C型失活成分。地尔硫卓可加快C型失活，但其不影响fKv1.4ΔN通道电流的激活过程。结论： 地尔硫卓为fKv1.4ΔN通道的开放状态阻滞剂，可加快Kv1.4ΔN通道的失活过程。

Abstract:

AIM:To examine the effects of diltiazem, an L-type Ca2+ channel blocker, on the activation and inactivation kinetics of fKv1.4, a potassium channel that generates the cardiac transient outward potassium current. METHODS: cRNA of fKv1.4ΔN, an N-terminal deleted mutant of the ferret Kv1.4 potassium channel, was injected into Xenopus oocytes to express the fKv1.4ΔN channel in cells. Currents were recorded using a two-electrode voltage clamp technique. RESULTS: Diltiazem (10 μmol/L to 1 000 μmol/L) blocked the fKv1.4ΔN channel in a frequency-dependent, voltage-dependent and concentration-dependent manner, suggesting an open channel block. IC50 was (241.04±23.06) μmol/L for fKv1.4Δ N channel at +50 mV. After application of diltiazem, fKv1.4 ΔN inactivation was bi-exponential, with a faster portion (drug-induced inactivation) and a slower portion (C-type inactivation). Diltiazem increased C-type inactivation rate. However, diltiazem did not shift fKv1.4ΔN steady activation curves. CONCLUSION: Diltiazem accelerates the inactivation of Kv1.4ΔN channel by binding to the open state of the channel.

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备注/Memo

备注/Memo:

收稿日期：2013-03-15.通讯作者：张冬，副主任医师，主要从事心律失常的研究 Email：highlight@aliyun.com

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更新日期/Last Update: 2013-09-30