hERG1a突变H70R对hERG1a单源四聚体和hERG1a/hERG1b二源四聚体通道功能的影响

被引：0
|
作者：
冯莉
杨佳雪
李新
贾长琪
蒋晨曦
机构：
[1] 首都医科大学附属北京安贞医院心内科
来源：
首都医科大学学报 | 2022年 / 43卷 / 05期
关键词：
快速延迟整流钾离子通道; 长QT综合征; H70R; hERG1a; hERG1b;
D O I：
暂无
中图分类号：
R541.7 [心律失常];
学科分类号：
摘要：
目的 本研究拟探索KCNH2编码心肌细胞快速延迟整流钾离子通道(rapidly activating delayed rectifier K+ channel, IKr)α亚基（the human ether-à-go-go-related gene, hERG）转录产物——hERG1a特有突变H70R对hERG1a单源四聚体通道(IhERG1a)及hERG1a/hERG1b二源四聚体通道(IhERG1a/hERG1b)功能的影响，明确是否存在差异。方法 以脂质体转染技术通过HEK293细胞表达可疑致病突变。应用全细胞膜片钳技术分别记录IhERG1a、IhERG1a/hERG1b电流。结果 H70R对IhERG1a/hERG1b电流密度抑制较IhERG1a更为显著（61%vs 42%;P<0.001）;且至稳态激活曲线左移，显著降低半激活电压（P<0.05）;H70R对IhERG1a和IhERG1a/hERG1b通道灭活动力学无显著影响（P>0.05）,IhERG1a/hERG1b较IhERG1a灭活显著加快（P>0.05）。结论 H70R对IhERG1a及IhERG1a/hERG1b通道功能影响趋势一致，但对IhERG1a/hERG1b通道电流抑制更为显著，IhERG1a/hERG1b较IhERG1a灭活显著加快，提示在hERG相关临床致病突变研究中应重视IhERG1a/hERG1b通道功能的改变。
引用
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页码：747 / 753
页数：7
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