Open AccessQT c interval and ventricular action potential prolongation in the Mecp2 Null/ + murine model of Rett syndrome
Author(s) -
Cheng Hongwei,
Charles Ian,
James Andrew F.,
Abdala Ana P.,
Hancox Jules C.
Publication year - 2022
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.15437
Subject(s) - rett syndrome , qt interval , mecp2 , long qt syndrome , medicine , repolarization , myocyte , sudden death , cardiology , ventricular action potential , prolongation , endocrinology , biology , electrophysiology , genetics , gene , phenotype
Abstract 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 I Na,Late inhibitor GS‐6615 (eleclazine; 10 μM) 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.