Ca(2+)-activated Cl(-) current is antiarrhythmic by reducing both spatial and temporal heterogeneity of cardiac repolarization.
Ca(2+)-activated Cl(-) current is antiarrhythmic by reducing both spatial and temporal heterogeneity of cardiac repolarization.
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Ca（2+） - 激活的Cl（ - ）电流是通过降低心脏复极化的空间和时间异质性，是抗心律失常。
DOI：
10.1016/j.yjmcc.2017.06.014
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发表时间：
2017-08
影响因子：
5
通讯作者：
Szentandrássy N
中科院分区：
文献类型：
--
作者：
Hegyi B;Horváth B;Váczi K;Gönczi M;Kistamás K;Ruzsnavszky F;Veress R;Izu LT;Chen-Izu Y;Bányász T;Magyar J;Csernoch L;Nánási PP;Szentandrássy N
钙激活的Cl-−电流(ICl(Ca))在心律失常中的作用仍存在争议。它可以在钙超载的细胞中产生延迟的后除极，而在其他研究中，ICL(Ca)减少了早期后除极(EAD)的发生率。因此，我们的目标是研究ICL(Ca)在心脏复极和EAD形成的时空异质性中的作用。实验在分离的犬左室不同部位的心肌细胞上进行，心外膜下细胞、中层心肌细胞和心内膜下细胞，以及中层心肌的心尖细胞和基底细胞。ICl(Ca)可被0.5 mm ol/L的9-蒽羧酸(9-AC)阻断。动作电位(AP)变化采用锐化微电极记录。分别用方波脉冲电压钳和AP电压钳(APVC)测量全细胞9-AC敏感电流。Western印迹法检测介导ICL(Ca)的离子通道蛋白TMEM16A和Bestrophin-3的蛋白表达。9-AC可降低受试细胞的1相复极化。除心外膜下细胞外，9-AC还以逆速率依赖的方式延长AP时程。方波脉冲记录的ICL(Ca)密度和TMEM16A和Bestrophin-3蛋白的标准化表达在被检查的细胞组之间都没有显著差异。在APVC环境下，心外膜下ICL(Ca)的早期外向成分显著大于心内膜下细胞。与应用典型心内膜下AP的实验相比，应用典型的心外膜下AP作为命令脉冲，在心外膜下和心内膜下细胞中都产生了显著更大的早期外向成分。用9-AC抑制ICL(Ca)在低刺激率下产生EADS，而刺激β-肾上腺素能时EADs的发生率增加。9-AC也增加了复极的短期变异性。我们认为ICL(Ca)通过减少心脏复极和EAD形成的时空异质性，对心律失常的风险具有保护作用。
The role of Ca2+-activated Cl− current (ICl(Ca)) in cardiac arrhythmias is still controversial. It can generate delayed afterdepolarizations in Ca2+-overloaded cells while in other studies incidence of early afterdepolarization (EAD) was reduced by ICl(Ca). Therefore our goal was to examine the role of ICl(Ca) in spatial and temporal heterogeneity of cardiac repolarization and EAD formation. Experiments were performed on isolated canine cardiomyocytes originating from various regions of the left ventricle; subepicardial, midmyocardial and subendocardial cells, as well as apical and basal cells of the midmyocardium. ICl(Ca) was blocked by 0.5 mmol/L 9-anthracene carboxylic acid (9-AC). Action potential (AP) changes were tested with sharp microelectrode recording. Whole-cell 9-AC-sensitive current was measured with either square pulse voltage-clamp or AP voltage-clamp (APVC). Protein expression of TMEM16A and Bestrophin-3, ion channel proteins mediating ICl(Ca), was detected by Western blot. 9-AC reduced phase-1 repolarization in every tested cell. 9-AC also increased AP duration in a reverse rate-dependent manner in all cell types except for subepicardial cells. Neither ICl(Ca) density recorded with square pulses nor the normalized expressions of TMEM16A and Bestrophin-3 proteins differed significantly among the examined groups of cells. The early outward component of ICl(Ca) was significantly larger in subepicardial than in subendocardial cells in APVC setting. Applying a typical subepicardial AP as a command pulse resulted in a significantly larger early outward component in both subepicardial and subendocardial cells, compared to experiments when a typical subendocardial AP was applied. Inhibiting ICl(Ca) by 9-AC generated EADs at low stimulation rates and their incidence increased upon beta-adrenergic stimulation. 9-AC increased the short-term variability of repolarization also. We suggest a protective role for ICl(Ca) against risk of arrhythmias by reducing spatial and temporal heterogeneity of cardiac repolarization and EAD formation.
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影响因子：
37.8
作者：
Fishman GI;Chugh SS;Dimarco JP;Albert CM;Anderson ME;Bonow RO;Buxton AE;Chen PS;Estes M;Jouven X;Kwong R;Lathrop DA;Mascette AM;Nerbonne JM;O'Rourke B;Page RL;Roden DM;Rosenbaum DS;Sotoodehnia N;Trayanova NA;Zheng ZJ
通讯作者：
Zheng ZJ
影响因子：
20.1
作者：
LIU, DW;GINTANT, GA;ANTZELEVITCH, C
通讯作者：
ANTZELEVITCH, C
影响因子：
5
作者：
Johnson, Daniel M.;Heijman, Jordi;Volders, Paul G. A.
通讯作者：
Volders, Paul G. A.
影响因子：
10.8
作者：
Szentadrassy, N;Banyasz, T;Nanasi, PP
通讯作者：
Nanasi, PP
影响因子：
6.1
作者：
Baumert, Mathias;Porta, Alberto;Volders, Paul G. A.
通讯作者：
Volders, Paul G. A.