Abstract
Short QT syndrome (SQTS) is a genetic arrhythmogenic disease that can cause malignant arrhythmia and sudden cardiac death. The current therapies for SQTS have application restrictions. We previously found that Mg· (NH2CH2CH2SO3)2· H2O, a taurine-magnesium coordination compound (TMCC) exerted anti-arrhythmic effects with low toxicity. In this study we established 3 different models to assess the potential anti-arrhythmic effects of TMCC on type 2 short QT syndrome (SQT2). In Langendorff guinea pig-perfused hearts, perfusion of pinacidil (20 μmol/L) significantly shortened the QT interval and QTpeak and increased rTp-Te (P<0.05 vs control). Subsequently, perfusion of TMCC (1–4 mmol/L) dose-dependently increased the QT interval and QTpeak (P<0.01 vs pinacidil). TMCC perfusion also reversed the rTp-Te value to the normal range. In guinea pig ventricular myocytes, perfusion of trapidil (1 mmol/L) significantly shortened the action potential duration at 50% (APD50) and 90% repolarization (APD90), which was significantly reversed by TMCC (0.01–1 mmol/L, P<0.05 vs trapidil). In HEK293 cells that stably expressed the outward delayed rectifier potassium channels (IKs), perfusion of TMCC (0.01–1 mmol/L) dose-dependently inhibited the IKs current with an IC50 value of 201.1 μmol/L. The present study provides evidence that TMCC can extend the repolarization period and inhibit the repolarizing current, IKs, thereby representing a therapeutic candidate for ventricular arrhythmia in SQT2.
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Acknowledgements
The authors appreciate the valuable comments from other members of our laboratories. This study was supported by the National Natural Science Foundation of China (No 81373410) and the Youth Project of Tianjin Natural Foundation, China (No 14JCQNJC13700).
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An, My., Sun, K., Li, Y. et al. Therapeutic effects of a taurine-magnesium coordination compound on experimental models of type 2 short QT syndrome. Acta Pharmacol Sin 39, 382–392 (2018). https://doi.org/10.1038/aps.2017.86
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DOI: https://doi.org/10.1038/aps.2017.86
