Ciencia

Acta Physiologica Sinica, October 25, 2004, 56 (5): 573-578
http://www.actaps.com.cn

573

Research Paper

Effect of chronic cigarette smoking on large-conductance calciumactivated potassium channel and Kv1.5 expression in bronchial smooth
muscle cells of rats
YE Hong1,2,*, MA Wan-Li2, YANG Mu-Lan3, LIU Sheng-Yuan1, WANG Di-Xun1
1

Department of Pathophysiology and 3pathology, TongjiMedical College, HuaZhong University of Science and Technology, Pulmonary

Disease Laboratory, Ministry of Health of China, Wuhan 430030, China;2Department of Respiratory medicine, Xiehe hospital, Tongji
Medical College, HuaZhong University of Science and Technology, Wuhan 430030, China.
Abstract: To investigate the role of potassium channels in the pathogenesis of airway hyperresponsivenessinduced by cigarette
smoking, the alteration in expression of large–conductance calcium-activated potassium channel (BKca) and voltage-dependent delayed
rectifier potassium channel (Kv1.5) in bronchial smooth muscle cells were investigated in chronic cigarette smoking rats. Airway
responsiveness was determined, hematoxylin and eosin staining, immuno-histochemistry, in-situ h ybridization andwestern blot
techniques were used. The results showed: (1) Chronic cigarette smoking down-regulated the protein synthesis and mRNA expression
of BKca and Kv1.5 in bronchial and bronchiolar smooth muscles. (2) BKca decreased more markedly than Kv1.5 in bronchi, but there
was no difference between them in bronchioli. (3) No changes in the expression of these two potassium channel proteins were foundin
extracted cell membrane protein from lung tissue. The results suggest that chronic cigarette smoking can down-regulate the levels of
BKca and Kv1.5 in rat bronchial smooth muscle cells in vivo, which might contribute to the mechanism of airway hyperresponsiveness
induced by cigarette smoking.
Key words: cigarette smoking; bronchial smooth muscle cells; potassium channel慢性吸烟大鼠气道平滑肌大电导的钙激活钾通道和 K v 1. 5 表达的变化
叶 红 1,2,*, 马万里 2, 杨木兰 3, 刘声远 1, 王迪浔 1
1

华中科技大学同济医学院病理生理系, 卫生部呼吸系疾病重点实验室; 2 华中科技大学同济医学院附属协和医院呼吸内科;

3

华

中科技大学同济医学院病理系, 武汉 430030
摘 要 : 复制大鼠的慢性吸烟模型，采用气道反应性的测定、HE 染色、免疫组织化学染色、原位杂交和免疫印迹实验等方
法，观察吸烟对大鼠支气管平滑肌大电导的钙激活的钾通道(BKca)和电压依赖性延迟整流钾通道 Kv1.5 蛋白和 mRNA 表达的影
响，以阐明吸烟引起的气道高反应性发病机制中钾通道表达变化的作用。结果显示： 慢性吸烟可降低大鼠大气道和小气道
(1)
BKca 和 Kv1.5 蛋白和 mRNA 表达； 大气道 BKca 的降低程度大于 Kv1.5, 小气道 BKca 和 Kv1.5 的降低程度无明显差异；
(2)(3)
吸烟对全肺组织 BKca 和 Kv1.5 的蛋白表达无明显影响。上述结果提示, 慢性吸烟可下调大鼠气道平滑肌钾通道 BKca 和 Kv1.5
的表达水平, 是导致气道高反应的机制之一。
关键词: 吸烟; 支气管平滑肌; 钾通道
中图分类号: Q 473; R363

Cigarette smoking is one of the most important risk
factors for human health. The oxidants of cigarette smoke
can induce airway damage, leading to chronic airway inReceived 2004-02-26

flammation and airway hyperresponsiveness (AHR). AHR
means thatthe airway is liable to constrict in response to
non-specific stimulation[1]. Chronic airway inflammation,

Accepted 2004-04-15

This work was supported by the National Natural Science Foundation of China (No.39770309).
*

Corresponding author. Tel: +86-27-83692654; Fax: +86-27-83692608; E-mail: yehongmwl@hotmail.com

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airway remodeling and the changes in the nature of smoothmuscle cells are important mechanisms of AHR induced
by cigarette smoking, of which most investigations focused on the damage of airway epithelial cells, but seldom
on the changes of bronchial smooth muscle cells.
Potassium channels are critical to the resting potential
and excitability of the cells. There are at least three types
of potassium channels in airway smooth muscle cells
(ASMC):delayed rectifier potassium channel (Kv), largeconductance calcium-activated potassium channel (BKca),
and ATP-sensitive potassium channel (KATP) , Kv1.5 is the
most important Kv regulating ASMC tension. Both BKca
and Kv1.5 are redundant in ASMC, they are very important in the maintenance of resting potential and resting tension[2,3]. The decrease in the activity...