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Activation of CLC‐3 Chloride Channels During Myocardial Ischemia Limits Prolongation of Q‐T and Effective Refractory Period
Author(s) -
Yu Ying,
Ye Lingyu Linda,
Li YiGang,
Duan Dayue Darrel
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.940.6
Subject(s) - refractory period , medicine , ischemia , intracardiac injection , cardiology , effective refractory period , electrophysiology , myocardial infarction , refractory (planetary science) , anesthesia , biology , astrobiology
Ischemia causes myocardial infarction and arrhythmias, such as Q‐T prolongation which leads to fatal ventricular arrhythmia. 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. Hypothesis CLC‐3 up‐regulation may shorten action potential during, Q‐T interval, and effective refractory period (ERP)under ischemic conditions. Methods In vivo surface electrocardiography (ECG) and intracardiac electrophysiology (ICEP) were used to compare the electrophysiological properties of age‐matched wild‐type (Clcn3+/+) and heart‐specific overexpression of human short CLC‐3 isoform (hsCLC‐3OE) mice under control and myocardial ischemia‐reperfusion conditions. Results Q‐T and Q‐Tc intervals of hsCLC‐3OE mice were significant shorter than those of Clcn3+/+ mice under control, ischemia and reperfusion conditions. In the ICEP, ventricular effective refractory period (VERP) of hsCLC‐3OE 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‐3OE 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 block point (AVBP, 91.13±4.08 ms) and 2:1 AVBP (71.3±3.8 ms) of hsCLC‐3OE 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‐3OE and Clcn3+/+ mice were observed under reperfusion conditions. Conclusions Up‐regulation of CLC‐3 may limit the ischemia‐induced Q‐T and ERP prolongation and postpone the advancements of Wenckebach and 2:1 AVBP. CLC‐3 up‐regulation may serve as an important adaptive mechanism against myocardial ischemia. Support or Funding Information This study was supported by National Heart, Lung, and Blood Institute Grant R01 #HL63914, #HL113598, R21 HL106252, AHA Western State Affiliate Grant‐in‐Aid #11GRNT7610161 (to D.D.D.), and National Natural Science Foundation of China (#81070154 and #81270258 to Y.G.L.).