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

Effect of Kv1.3 and K_(Ca)3.1 potassium ion channels on the proliferation and migration of monocytes/macrophages

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,结果显示,分别用KCa3.1特异性阻断剂TRAM-34和Kv1.3强效阻断剂Sh K阻断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;Sh K使单核/巨噬细胞增殖受到显著抑制。用TRAM-34和Sh K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。

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 monocytes/macrophages on inflammatory monocyte chemotaxis. Chemotaxis assay was used to test the inflammatory Ly-6Chi monocyte chemotaxis caused by the monocytes/macrophages. The proliferation of monocytes/macrophages was detected by cell counting kit-8 （CCKS）. Enzyme-linked immunosorbent assay （ELISA） was applied to detect the C-C motif ligand 7 （CCL7） in cultured media. The results showed that the recruitment of Ly-6Chi monocyte induced by monocytes/macrophages was suppressed by the potent Kv1.3 blocker Stichodactyla helianthus neurotoxin （ShK） or the specific Kca3,1 inhibitor TRAM-34. Meanwhile, the proliferation of monocytes/macrophages was significantly inhibited by ShK. The response of Ly-6Chi monocyte pretreated with ShK or TRAM-34 to CCL2 was declined. These results suggest that Kca3.1 and Kvh3 may play an important role in monocytes/macrophages＇ proliferation and migration.