Complementarity between Arrhythmia Mechanisms Found in Silico and in Genetic Models of N588K-hERG Linked Short QT Syndrome

Author Info

Chunyun Du Henggui Zhang Jules Hancox Yihong Zhang

Corresponding Author

Jules Hancox
School of Physiology, Pharmacology and Neuroscience, Medical Sciences Building, University Walk, University of Bristol, BS8 1TD, United Kingdom

A B S T R A C T

Congenital Short QT Syndrome (SQTS) is a rare but dangerous condition involving abbreviated ventricular repolarization and an increased risk of atrial and ventricular arrhythmias. Taking the example of the first identified SQTS mutation, N588K-hERG, we consider briefly the basic science approaches used to obtain an understanding of the mechanism(s) of arrhythmogenesis in this form of the syndrome. A combination of recombinant channel electrophysiology and in silico simulations has provided insights into causality between the identified mutation, accelerated repolarization and increased susceptibility to re-entry in N588K-hERG-linked SQTS. Subsequent studies employing a transgenic rabbit model or human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) have further demonstrated mechanisms predisposing to re-entry, spiral wave activity and arrhythmia in intact tissue. The complementarity between the findings made using these different approaches gives confidence that, collectively, they have identified major arrhythmia mechanisms and their potential mitigation by Class I antiarrhythmic drugs in this form of SQTS.

Article Info

Article Type

Review Article

Publication history

Received: Fri 06, Mar 2020
Accepted: Sat 21, Mar 2020
Published: Mon 30, Mar 2020

Copyright

© 2023 Jules Hancox. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Hosting by Science Repository.
DOI: 10.31487/j.JICOA.2020.01.13