Concomitant SK current activation and sodium current inhibition cause J wave syndrome

被引：19

作者：

Chen, Mu ^{[1
,2
,3
]}

Xu, Dong-Zhu ^{[1
,2
,4
]}

Wu, Adonis Z. ^{[1
,2
]}

Guo, Shuai ^{[1
,2
,5
]}

Wan, Juyi ^{[1
,2
,6
]}

Yin, Dechun ^{[1
,2
,5
]}

Lin, Shien-Fong ^{[1
,2
,7
]}

Chen, Zhenhui ^{[1
,2
]}

Rubart-von der Lohe, Michael ^{[1
,2
,8
]}

Everett, Thomas H. ^{[1
,2
]}

Qu, Zhilin ^{[9
,10
]}

Weiss, James N. ^{[9
,10
]}

Chen, Peng-Sheng ^{[1
,2
]}

机构：

[1] Indiana Univ Sch Med, Krannert Inst Cardiol, Indianapolis, IN 46202 USA

[2] Indiana Univ Sch Med, Div Cardiol, Dept Med, Indianapolis, IN 46202 USA

[3] Shanghai Jiao Tong Univ, Dept Cardiol, Xinhua Hosp, Sch Med, Shanghai, Peoples R China

[4] Univ Tsukuba, Cardiovasc Div, Inst Clin Med, Fac Med, Tsukuba, Ibaraki, Japan

[5] Harbin Med Univ, Affiliated Hosp 1, Dept Cardiol, Harbin, Heilongjiang, Peoples R China

[6] Southwest Med Univ, Affiliated Hosp, Dept Cardiothorac Surg, Luzhou, Peoples R China

[7] Natl Chiao Tung Univ, Inst Biomed Engn, Coll Elect & Comp Engn, Hsinchu, Taiwan

[8] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA

[9] Univ Calif Los Angeles, Dept Med Cardiol, Los Angeles, CA USA

[10] Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90024 USA

来源：

JCI INSIGHT | 2018年 / 3卷 / 22期

关键词：

CA2+-ACTIVATED K+ CHANNEL; POTASSIUM CURRENT; VENTRICULAR-ARRHYTHMIAS; ALLOSTERIC MODULATOR; BRUGADA SYNDROME; REPOLARIZATION; TEMPERATURE; INCREASES; VOLTAGE; ROLES;

D O I：

10.1172/jci.insight.122329

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The mechanisms of J wave syndrome (JWS) are incompletely understood. Here, we showed that the concomitant activation of small-conductance calcium-activated potassium (SK) current (I-KAS) and inhibition of sodium current by cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA) recapitulate the phenotypes of JWS in Langendorff-perfused rabbit hearts. CyPPA induced significant J wave elevation and frequent spontaneous ventricular fibrillation (SVF), as well as sinus bradycardia, atrioventricular block, and intraventricular conduction delay. I-KAS activation by CyPPA resulted in heterogeneous shortening of action potential (AP) duration (APD) and repolarization alternans. CyPPA inhibited cardiac sodium current (I-Na) and decelerated AP upstroke and intracellular calcium transient. SVFs were typically triggered by short-coupled premature ventricular contractions, initiated with phase 2 reentry and originated more frequently from the right than the left ventricles. Subsequent I-KAS blockade by apamin reduced J wave elevation and eliminated SVF. beta-Adrenergic stimulation was antiarrhythmic in CyPPA-induced electrical storm. Like CyPPA, hypothermia (32.0 degrees C) also induced J wave elevation and SVF. It facilitated negative calcium-voltage coupling and phase 2 repolarization alternans with spatial and electromechanical discordance, which were ameliorated by apamin. These findings suggest that I-KAS activation contributes to the development of JWS in rabbit ventricles.

引用

页数：16

共 46 条

[21] DIFFERENCES IN THE ELECTROPHYSIOLOGICAL RESPONSE OF CANINE VENTRICULAR EPICARDIUM AND ENDOCARDIUM TO ISCHEMIA - ROLE OF THE TRANSIENT OUTWARD CURRENT [J].