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阻断Kv1.3和KCa3.1钾通道对单核/巨噬细胞增殖和趋化功能的影响

张双霞, 王宪沛, 高传玉, 鞠晨晖, 朱利杰, 杜以梅

郑州大学人民医院心内科，郑州 450003；华中科技大学同济医学院附属协和医院心内科，离子通道病研究中心，武汉 430000

摘要

电压门控钾通道Kv1.3和钙激活钾通道KCa3.1是单核/巨噬细胞上的两种钾通道。本文旨在研究阻断Kv1.3和KCa3.1钾通道对于单核/巨噬细胞增殖和趋化功能的影响。用趋化实验检测单核/巨噬细胞对Ly-6Chi单核细胞(炎症型单核细胞)的趋化作用，用CCK8试剂盒检测单核/巨噬细胞的增殖情况，用ELISA法检测趋化因子CCL7的浓度变化，用趋化实验检测趋化因子CCL2和CCL7对炎症型单核细胞的趋化作用。结果显示，用KCa3.1特异性阻断剂TRAM-34和Kv1.3强效阻断剂ShK阻断了这两种钾离子通道后，单核/巨噬细胞对Ly-6Chi单核细胞的趋化能力降低，增殖受到抑制，分泌的趋化因子CCL7浓度下降。用TRAM-34和ShK孵育过的Ly-6Chi单核细胞对CCL2的敏感性下降。以上结果提示，Kv1.3和KCa3.1钾通道在单核/巨噬细胞活化、增殖和趋化过程起重要作用，这两种钾通道有望成为自身免疫性疾病和急性心肌梗死后心肌重塑调节的靶点。

关键词： 单核/巨噬细胞; KCa3.1钾通道; Kv1.3钾通道; Ly-6Chi单核细胞

分类号：R392.5

[Effect of Kv1.3 and KCa3.1 potassium ion channels on the proliferation and migration of monocytes/macrophages.] [Article in Chinese]

ZHANG Shuang-Xia, WANG Xian-Pei, GAO Chuan-Yu, JU Chen-Hui, ZHU Li-Jie, DU Yi-Mei

Department of Cardiology, Zhengzhou University People’s Hospital, Zhengzhou 450003, China； Research Center of Ion Channelopathy, Institute of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China

Abstract

This study was aimed to investigate the effects of blockade of Ca2+ activated channel KCa3.1 and voltage-gated potassium channel Kv1.3 of the mononuclear/macrophages on inflammatory monocyte chemotaxis. Chemotaxis assay was used to test the inflammatory Ly-6Chi monocyte chemotaxis caused by the mononuclear/macrophages. The proliferation of mononuclear macrophages was detected by cell counting kit-8 (CCK8). Enzyme-linked immunosorbent assay (ELISA) was applied to detect the C-C motif ligand 7 (CCL7) in cultured media. The results showed that the proliferation of mononuclear/macrophages and the recruitment of Ly-6Chi monocyte induced by mononuclear/macrophages were suppressed by the potent Kv1.3 blocker Stichodactyla helianthustoxin (ShK) and the specific KCa3.1 inhibitor TRAM-34. Meanwhile the secretion of CCL7 from mononuclear/macrophages was decreased. The response of Ly-6Chi monocyte pretreated with ShK or TRAM-34 to CCL2 was declined. These results suggest that KCa3.1 and Kv1.3 may play an important role in mononuclear macrophages’ proliferation and migration.

Key words: mononuclear/macrophages; KCa3.1 potassium ion channel; Kv1.3 potassium ion channel; Ly-6Chi monocytes

收稿日期：2015-03-14　　录用日期：2015-05-20

通讯作者：高传玉　　E-mail: gaocy6802@163.com

引用本文：

张双霞, 王宪沛, 高传玉, 鞠晨晖, 朱利杰, 杜以梅. 阻断Kv1.3和KCa3.1钾通道对单核/巨噬细胞增殖和趋化功能的影响[J]. 生理学报 2015; 67 (5): 505-512.

ZHANG Shuang-Xia, WANG Xian-Pei, GAO Chuan-Yu, JU Chen-Hui, ZHU Li-Jie, DU Yi-Mei. [Effect of Kv1.3 and KCa3.1 potassium ion channels on the proliferation and migration of monocytes/macrophages.] [Article in Chinese]. Acta Physiol Sin 2015; 67 (5): 505-512 (in Chinese with English abstract).