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

Short QT Syndrome (SQTS)is an identified genetic arrhythmogenic disease associated with abnormally abbreviated QT intervals and an increased susceptibility to malignant arrhythmia and sudden cardiac death (SCD). SQT2 variant (linked to slow delayed rectifier, IKs) of SQTS, results from a gain-of-function (V307L) in the KCNQ1 subunit of the IKschannel. Pro-arrhythmogenic effects of SQT2 have been well characterized, but less is known about the pharmacological treatment of SQT2. We find that taurine-magnesium coordination compound (TMCC)exerted anti-arrhythmic effects with low toxicity. Therefore, this study aimed to assess the potential effects of TMCC on SQT2. The channel-blocking effect of TMCC on IKsin healthy and SQT2 cells were incorporated into computer models ofhuman ventricular action potential (AP) and into one dimensional transmural tissue simulations. In the single-cell model, TMCC prolonged cell AP duration at 90% repolarization (APD90). In the one dimensionalintact model, TMCC prolonged the QT interval on the pseudo-ECGs. Thus, the present study provides evidence that TMCC can extend the repolarization period and APD90and QT interval, thereby representing a therapeutic candidate for arrhythmia in SQT2.