INTERNATIONAL JOURNAL OF CARDIOLOGY | 卷:214 |
Heart-specific overexpression of the human short CLC-3 chloride channel isoform limits myocardial ischemia-induced ERP and QT prolongation | |
Article | |
Yu, Ying1,2,3  Ye, Linda2,3  Li, Yi-Gang1  Burkin, Dean J.3  Duan, Dayue Darrel2,3  | |
[1] Shanghai Jiao Tong Univ, Xinhua Hosp, Dept Cardiol, Sch Med, 19 Suite 932,1665 Kongjiang Rd, Shanghai 200092, Peoples R China | |
[2] Univ Nevada, Sch Med, Lab Cardiovasc Phenom, Reno, NV 89557 USA | |
[3] Univ Nevada, Dept Pharmacol, Sch Med, Reno, NV 89557 USA | |
关键词: Arrhythmia; Torsade de pointes; Electrophysiology; Ion channels; ECG; Ischemia; Chloride channels; | |
DOI : 10.1016/j.ijcard.2016.03.191 | |
来源: Elsevier | |
【 摘 要 】
Introduction: Ischemia causes myocardial infarction and arrhythmias. Up-regulation of cardiac CLC-3 chloride channels is important for ischemic preconditioning-induced second-window protection against myocardial infarction. But its consequences in ischemia-induced electrical remodeling are still unknown. Methods: The recently-characterized heart-specific overexpression of human short CLC-3 isoform (hsCLC-3(OE)) mice was used to study the effects of CLC-3 up-regulation on cardiac electrophysiology under ischemia/reperfusion conditions. In vivo surface electrocardiography (ECG) and intracardiac electrophysiology (ICEP) were used to compare the electrophysiological properties of age-matched wild-type (Clcn3(+/+)) and hsCLC-3(OE) mice under control and myocardial ischemia-reperfusion conditions. Results: QT and QTc intervals of hsCLC-3(OE) mice were significantly shorter than those of Clcn3(+/+) mice under control, ischemia and reperfusion conditions. In the ICEP, ventricular effective refractory period (VERP) of hsCLC-3(OE) mice (26.7 +/- 1.7 ms, n = 6) was significantly shorter than that of Clcn3(+/+) mice (36.9 +/- 2.8 ms, n = 8, P < 0.05). Under ischemia condition, both VERP (19.8 +/- 1.3 ms) and atrial effective refractory period (AERP, 34.8 +/- 2.5 ms) of hsCLC-3(OE) mice were significantly shorter than those of Clcn3(+/+) mice (35.2 +/- 3.0 ms and 45.8 +/- 1.6 ms, P < 0.01, respectively). Wenckebach atrioventricular nodal block point (AVBP, 91.13 +/- 4.08 ms) and 2: 1 AVBP (71.3 +/- 3.8 ms) of hsCLC-3(OE) mice were significantly shorter than those of Clcn3(+/+) mice (102.0 +/- 2.0 ms and 84.1 +/- 2.8 ms, P < 0.05, respectively). However, no differences of ICEP parameters between hsCLC-3(OE) and Clcn3(+/+) mice were observed under reperfusion conditions. Conclusion: Heart-specific overexpression of hsCLC-3 limited the ischemia-induced QT and ERP prolongation and postponed the advancements of Wenckebach and 2:1 AVBP. CLC-3 up-regulation may serve as an important adaptive mechanism against myocardial ischemia. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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