Human KCNQ1 S140G mutation is associated with atrioventricular blocks
Human KCNQ1 S140G mutation is associated with atrioventricular blocks
复制标题
人类 KCNQ1 S140G 突变与房室传导阻滞相关
DOI：
10.1016/j.hrthm.2007.01.029
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发表时间：
2007-05-01
期刊：
影响因子：
5.5
通讯作者：
Chen, Yi Han
中科院分区：
文献类型：
--
作者：
Yang, Yiqing;Liu, Yi;Chen, Yi Han
BACKGROUND We recently reported that an S140G mutation in human KCNQ1, an alpha subunit of potassium channels, was involved in the pathogenesis of familial atrial fibrillation (AF), but it is not clear whether the mutation is associated with other cardiac arrhythmias.OBJECTIVE The purpose of this study was to further explore the association of the KCNQ1 S140G mutation with cardiac arrhythmias.METHODS We produced a transgenic mouse model with myocardium-specific expression of the human KCNQ1 S140G mutation under the control of an a-cardiac myosin heavy chain promoter by standard transgenic procedure and evaluated the relationship between the KCNQ1 mutation and its phenotypes in a human family.RESULTS Four Lines of transgenic mice were established with a high level of human KCNQ1 S140G expression in the heart. Frequent episodes of first-, second-, advanced-, or third-degree atrio-ventricular block (AVB) occurred in at least 65% of transgenic descendants from the four lines. However, none of the five wildtype transgenic Lines presented with AVBs. HMR1556, a KCNQ1-specific blocker, can terminate the AVBs. With the exception of at most three AF individuals, at Least 13 AF patients were found to show obviously stow ventricular response, which may be one manifestation of AVBs. Interestingly, AF was not detected in these transgenic mice.CONCLUSION The results suggest that human KCNQ1 S140G is also Likely to be a causative mutation responsible for AVBs. The transgenic mouse model is a potential tool to explore mechanisms of AVBs.
