Colchicine modulates calcium homeostasis and electrical property of HL-1 cells
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- 作者：Yen-Yu Lu ; Yao-Chang Chen ; Yu-Hsun Kao ; Yung-Kuo Lin ; Yung-Hsin Yeh ; Shih-Ann Chen and Yi-Jen Chen
- 刊名：Journal of Cellular and Molecular Medicine
- 出版年：2016
- 出版时间：June 2016
- 年：2016
- 卷：20
- 期：6
- 页码：1182-1190
- 全文大小：643K
- ISSN：1582-4934
文摘
Colchicine is a microtubule disruptor that reduces the occurrence of atrial fibrillation (AF) after an operation or ablation. However, knowledge of the effects of colchicine on atrial myocytes is limited. The aim of this study was to determine if colchicine can regulate calcium (Ca2+) homeostasis and attenuate the electrical effects of the extracellular matrix on atrial myocytes. Whole-cell clamp, confocal microscopy with fluorescence, and western blotting were used to evaluate the action potential and ionic currents of HL-1 cells treated with and without (control) colchicine (3 nM) for 24 hrs. Compared with control cells, colchicine-treated HL-1 cells had a longer action potential duration with smaller intracellular Ca2+ transients and sarcoplasmic reticulum (SR) Ca2+ content by 10% and 47%, respectively. Colchicine-treated HL-1 cells showed a smaller L-type Ca2+ current, reverse mode sodium–calcium exchanger (NCX) current and transient outward potassium current than control cells, but had a similar ultra-rapid activating outward potassium current and apamin-sensitive small-conductance Ca2+-activated potassium current compared with control cells. Colchicine-treated HL-1 cells expressed less SERCA2a, total, Thr17-phosphorylated phospholamban, Cav1.2, CaMKII, NCX, Kv1.4 and Kv1.5, but they expressed similar levels of the ryanodine receptor, Ser16-phosphorylated phospholamban and Kv4.2. Colchicine attenuated the shortening of the collagen-induced action potential duration in HL-1 cells. These findings suggest that colchicine modulates the atrial electrical activity and Ca2+ regulation and attenuates the electrical effects of collagen, which may contribute to its anti-AF activity.