期刊
PHYSIOLOGICAL REPORTS
卷 10, 期 19, 页码 -出版社
WILEY
DOI: 10.14814/phy2.15437
关键词
action potential; APD(90); eleclazine; GS-6615; MECP2; QT interval; ranolazine; repolarization; Rett syndrome; RTT
类别
资金
- British Heart Foundation [PG/16/55/32277]
This study investigates the ECG and ventricular action potential characteristics of Mecp2(Null/+) female mice. The results show prolonged QT intervals and delayed repolarization in Mecp2(Null/+) mice, and suggest the potential of GS-6615 as an intervention for QT prolongation in RTT.
Rett Syndrome (RTT) is a congenital, X-chromosome-linked developmental disorder characterized by developmental delay, dysautonomia, and breathing irregularities. RTT is also associated with sudden death and QT intervals are prolonged in some RTT patients. Most individuals with RTT have mutations in the MECP2 gene. Whilst there is some evidence for QT prolongation in mouse models of RTT, there is comparatively little information on how loss of Mecp2 function affects ventricular action potentials (APs) and, to-date, none on ventricular APs from female RTT mice. Accordingly, the present study was conducted to determine ECG and ventricular AP characteristics of Mecp2(Null/+) female mice. ECG recordings from 12-13 month old female Mecp2(Null/+) mice showed prolonged rate corrected QT (QTc) intervals compared to wild-type (WT) controls. Although Mecp2(Null/+) animals exhibited longer periods of apnoea than did controls, no correlation between apnoea length and QT(c) interval was observed. Action potentials (APs) from Mecp2(Null/+) myocytes had longer APD(90) values than those from WT myocytes and showed augmented triangulation. Application of the investigational INa,Late inhibitor GS-6615 (eleclazine; 10 mu M) reduced both APD(90) and AP triangulation in Mecp2(Null/+) and WT myocytes. These results constitute the first direct demonstration of delayed repolarization in Mecp2(Null/+) myocytes and provide further evidence that GS-6615 may have potential as an intervention against QT prolongation in RTT.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据