Action potential clamp and chloroquine sensitivity of mutant Kir2.1 channels responsible for variant 3 short QT syndrome.
Action potential clamp and chloroquine sensitivity of mutant Kir2.1 channels responsible for variant 3 short QT syndrome.
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DOI：
10.1016/j.yjmcc.2009.02.027
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发表时间：
2009-11
影响因子：
5
通讯作者：
Hancox, Jules C.
中科院分区：
文献类型：
--
作者：
El Harchi, Aziza;McPate, Mark J.;Zhang, Yi Hong;Zhang, Henggui;Hancox, Jules C.
最近发现的短QT综合征（SQTS）的遗传形式与心律失常和猝死的风险增加有关。SQT 3变体与KCNJ 2编码的Kir2.1 K+通道中的氨基酸取代（D172 N）相关。在本研究中，瞬时转染的中国人卵巢上皮细胞在37 °C下的全细胞动作电位（AP）钳记录显示，通过D172 N通道的外向Kir2.1电流显著增加，与心室和心房AP命令期间峰值复极电流的右移相关。氯喹对野生型Kir2.1、D172 N-Kir 2.1、WT和D172 N共表达细胞的IC 50分别为2.45 μM、3.30 μM和3.11 μM（P均> 0.05）。这些发现确立了氯喹作为SQT 3突变体Kir2.1通道的有效抑制剂。
Recently identified genetic forms of short QT syndrome (SQTS) are associated with an increased risk of arrhythmia and sudden death. The SQT3 variant is associated with an amino-acid substitution (D172N) in the KCNJ2-encoded Kir2.1 K+ channel. In this study, whole-cell action potential (AP) clamp recording from transiently transfected Chinese Hamster Ovary cells at 37 °C showed marked augmentation of outward Kir2.1 current through D172N channels, associated with right-ward voltage-shifts of peak repolarizing current during both ventricular and atrial AP commands. Peak outward current elicited by ventricular AP commands was inhibited by chloroquine with an IC50 of 2.45 μM for wild-type (WT) Kir2.1, of 3.30 μM for D172N-Kir2.1 alone and of 3.11 μM for co-expressed WT and D172N (P > 0.05 for all). These findings establish chloroquine as an effective inhibitor of SQT3 mutant Kir2.1 channels.
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影响因子：
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作者：
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通讯作者：
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