Ying Yu1, Linda Ye2, Yi-Gang Li3, Dean J Burkin4, Dayue Darrel Duan5. 1. Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China; Laboratory of Cardiovascular Phenomics, University of Nevada School of Medicine, Reno, NV 89557-0318, USA; Department of Pharmacology, University of Nevada School of Medicine, Reno, NV 89557-0318, USA. 2. Laboratory of Cardiovascular Phenomics, University of Nevada School of Medicine, Reno, NV 89557-0318, USA; Department of Pharmacology, University of Nevada School of Medicine, Reno, NV 89557-0318, USA. 3. Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China. Electronic address: drliyigang@outlook.com. 4. Department of Pharmacology, University of Nevada School of Medicine, Reno, NV 89557-0318, USA. 5. Laboratory of Cardiovascular Phenomics, University of Nevada School of Medicine, Reno, NV 89557-0318, USA; Department of Pharmacology, University of Nevada School of Medicine, Reno, NV 89557-0318, USA. Electronic address: dduan@medicine.nevada.edu.
Abstract
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±1.7ms, n=6) was significantly shorter than that of Clcn3(+/+) mice (36.9±2.8ms, n=8, P<0.05). Under ischemia condition, both VERP (19.8±1.3ms) and atrial effective refractory period (AERP, 34.8±2.5ms) of hsCLC-3(OE) mice were significantly shorter than those of Clcn3(+/+) mice (35.2±3.0ms and 45.8±1.6ms, P<0.01, respectively). Wenckebach atrioventricular nodal block point (AVBP, 91.13±4.08ms) and 2:1 AVBP (71.3±3.8ms) of hsCLC-3(OE) mice were significantly shorter than those of Clcn3(+/+) mice (102.0±2.0ms and 84.1±2.8ms, 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.
INTRODUCTION:Ischemia causes myocardial infarction and arrhythmias. Up-regulation of cardiac CLC-3chloride 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±1.7ms, n=6) was significantly shorter than that of Clcn3(+/+) mice (36.9±2.8ms, n=8, P<0.05). Under ischemia condition, both VERP (19.8±1.3ms) and atrial effective refractory period (AERP, 34.8±2.5ms) of hsCLC-3(OE) mice were significantly shorter than those of Clcn3(+/+) mice (35.2±3.0ms and 45.8±1.6ms, P<0.01, respectively). Wenckebach atrioventricular nodal block point (AVBP, 91.13±4.08ms) and 2:1 AVBP (71.3±3.8ms) of hsCLC-3(OE) mice were significantly shorter than those of Clcn3(+/+) mice (102.0±2.0ms and 84.1±2.8ms, 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.
Authors: Roberto J Diaz; Stephen C Armstrong; Michelle Batthish; Peter H Backx; Charles E Ganote; Gregory J Wilson Journal: J Mol Cell Cardiol Date: 2003-01 Impact factor: 5.000
Authors: Nathan D Bozeat; Sunny Yang Xiang; Linda L Ye; Tammy Y Yao; Marie L Duan; Dean J Burkin; Fred S Lamb; Dayue Darrel Duan Journal: Cell Physiol Biochem Date: 2011-12-16