title: Colchicine modulates calcium homeostasis and electrical property of HL-1 cells.
abstract: 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 (Ca(2+) ) 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 Ca(2+) transients and sarcoplasmic reticulum (SR) Ca(2+) content by 10% and 47%, respectively. Colchicine-treated HL-1 cells showed a smaller L-type Ca(2+) 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 Ca(2+) -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 Ca(2+) regulation and attenuates the electrical effects of collagen, which may contribute to its anti-AF activity.
authors.affiliation: Division of Cardiology, Sijhih Cathay General Hospital, New Taipei City, Taiwan.|School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Yen-Yu
authors.initials: YY
authors.lastname: Lu
authors.affiliation: Department of Biomedical Engineering, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yu-Hsun
authors.initials: YH
authors.lastname: Kao
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yung-Kuo
authors.initials: YK
authors.lastname: Lin
authors.affiliation: Cardiovascular Division, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Yung-Hsin
authors.initials: YH
authors.lastname: Yeh
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Division of Cardiology and Cardiovascular Research Center, Veterans General Hospital-Taipei, Taipei, Taiwan.
authors.forename: Shih-Ann
authors.initials: SA
authors.lastname: Chen
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Chen
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D003078:Colchicine / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology; D055724:Electrophysiological Phenomena / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D006706:Homeostasis / Q000187:drug effects*; D015640:Ion Channel Gating / Q000187:drug effects; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism
chemical_list: D015221:Potassium Channels; D021122:Protein Subunits; D003094:Collagen; D003078:Colchicine; D002118:Calcium
keywords: calcium handling; colchicine; electrophysiology