QTc interval and ventricular action potential prolongation in the Mecp2Null/+ murine model of Rett syndrome

QTc intervals and action potentials (APs) from ventricular myocytes were found to be prolonged in females from a murine model of Rett Syndrome (RTT). APs in ventricular myocytes from RTT mice were shortened by GS-6615, a late sodium current inhibitor. AbstractRett 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 theMECP2 gene. Whilst there is some evidence for QT prolongation in mouse models of RTT, there is comparatively little information on how loss ofMecp2 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 ofMecp2Null/+ female mice. ECG recordings from 12 –13 month old femaleMecp2Null/+ mice showed prolonged rate corrected QT (QTc) intervals compared to wild-type (WT) controls. AlthoughMecp2Null/+ animals exhibited longer periods of apnoea than did controls, no correlation between apnoea length and QTc interval was observed. Action potentials (APs) fromMecp2Null/+ myocytes had longer APD90 values than those from WT myocytes and showed augmented triangulation. Application of the investigational INa,Late inhibitor GS-6615 (eleclazine; 10  μM) reduced both APD90 and AP tr...
Source: Physiological Reports - Category: Physiology Authors: Tags: ORIGINAL ARTICLE Source Type: research