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不同年龄大鼠心肌细胞瞬时外向钾电流的变化

傅义程, 陈瑞, 陈美烟, 陈钰, 汪艳丽, 徐斌, 杨洁, 尹彤, 李泱^*

解放军总医院老年心血管病研究所，北京 100853

摘要

本文旨在研究心肌细胞瞬时外向钾电流(transient outward potassium current, Ito)的随龄变化及其药物反应性改变。Sprague Dawley大鼠28只，分为青年组(3~5月龄)、成年组(13~15月龄)和老年组(22~24月龄)。酶法分离心室肌细胞，应用全细胞膜片钳技术记录各组Ito。并于细胞外液分别加入1.0 μmol/L异丙肾上腺素和2.0 mmol/L 4-氨基吡啶干预，观察Ito的变化。结果显示，与青年组和成年组相比，老年组Ito电流密度显著增加。门控动力学研究显示，老年组Ito电流稳态激活曲线左移，通道关闭态失活速率明显降低，稳态失活后恢复速率加快，而稳态失活过程无明显变化。老年组Ito对选择性抑制剂4-氨基吡啶的反应性与青年组和成年组相似，但老年组Ito对β受体激动剂异丙肾上腺素的反应性却明显弱于青年组和成年组，各组电流密度分别增加55.9%、127.5%和125.8%。上述结果提示，随着大鼠年龄的增加，心肌细胞Ito电流密度显著升高，与通道门控的激活、关闭态失活和失活后恢复机制改变有关，且老年鼠Ito对异丙肾上腺素的反应性降低。

关键词： 大鼠; 心室肌细胞; 瞬时外向钾电流; 心律失常; 膜片钳技术

分类号：R329

[Age-related changes in transient outward potassium current of rat ventricular myocyte.] [Article in Chinese]

FU Yi-Cheng, CHEN Rui, Chen Mei-Yan, WANG Yan- Li, XU Bin, YANG Jie, YIN Tong, LI Yang

Institute of Geriatric Cardiology, the PLA General Hospital, Beijing 100853, China.

Abstract

The study aimed to investigate the age-related changes and drug reactions of transient outward potassium current (I(to)) of ventricular myocytes. Twenty-eight Sprague Dawley rats were divided into young (3-5 months), adult (13-15 months) and aged (22-24 months) groups, and I(to) currents of isolated myocytes from each group were recorded respectively by patch-clamp. The perfusion of 2.0 mmol/L 4-AP or 1.0 μmol/L isoproterenol was added respectively in each group, and the changes of I(to) were observed. In comparison with young and adult groups, I(to) densities of ventricular myocytes in aged group was significantly increased, the curve of steady-state activation of I(to) shifted to the left, the close-state inactivation rate significantly decreased, and recovery rate from the steady-state inactivation became quicker. However, no significant changes could be detected for the I(to) steady-state inactivation of ventricular myocytes in aged group. The similar responsiveness to 4-AP was observed in all three groups, but the responsiveness to isoproterenol was weaker in the aged group (55.9%) than in the other two groups (127.5% and 125.8%). In conclusion, the results show that I(to) of rat ventricular myocyte of aging heart has increased current density and decreased response to isoproterenol.

Key words: Rats; ventricular myocytes; transient outward potassium current; arrhythmia; patch clamp

收稿日期：2012-08-17　　录用日期：2013-03-04

通讯作者：李泱　　E-mail: liyangbsh@163.com

引用本文：

傅义程, 陈瑞, 陈美烟, 陈钰, 汪艳丽, 徐斌, 杨洁, 尹彤, 李泱. 不同年龄大鼠心肌细胞瞬时外向钾电流的变化[J]. 生理学报 2013; 65 (2): 185-192.

FU Yi-Cheng, CHEN Rui, Chen Mei-Yan, WANG Yan- Li, XU Bin, YANG Jie, YIN Tong, LI Yang. [Age-related changes in transient outward potassium current of rat ventricular myocyte.] [Article in Chinese]. Acta Physiol Sin 2013; 65 (2): 185-192 (in Chinese with English abstract).