Effects of Taurine-Magnesium Coordination Compound on Type 2 Short QT Syndrome: a Simulation Study

Cunjin Luo1, Dominic G. Whittaker2, Tong Liu3, Yacong Li4, Kuanquan Wang4, Ying He5, Henggui Zhang6
1Southwest Medical University, 2University of Nottingham, 3Tianjin Medical University, 4Harbin Institute of Technology, 5De Montfort University, 6The University of Manchester


Background: The short QT syndrome (SQTS) is rare inherited channelopathy associated with marked shortening of QT interval resulting from an accelerated cardiac repolarization. Patients are prone to atrial and ventricular tachyarrhythmia and have a high risk for sudden cardiac death (SCD). The SQT2, SQTS variant, results from a gain-of-function V307L-KCNQ1 mutation in the rapid delayed rectifier potassium current (IKs) channels. Previous studies showed that Taurine-Magnesium Coordination Compound (TMCC) can block IKs current, here we used in silico approach to evaluate TMCC’s electrophysiological effects on SQT2.

Methods and Resutls: Contemporary mathematical models of human ventricular action potential (AP) developed by ten Tusscher et al. were modified to incorporate a modified formulation of IKs describing the SQT2 mutant condition. Cellular action potential models were incorporated into a transmural strand for investigation of QT interval changes. In addition, the simulated TMCC to prolong the QT interval in SQT1 condition was quantified. The blocking effects of TMCC on IKs were modelled by using Hill coefficient and IC50 from literatures (0.01, 0.1 and 1 mM TMCC decreased the peak of IKs by 27.99%, 48.18% and 60.13%). At the single cells, TMCC prolonged the action potential duration (APD) in SQT2 condition; at the strand level, the effects of TMCC normalized the QT interval in SQT2.

Conclusions: Simulation results identified TMCC as a potential drug of choice for SQTS treatment.