Therapeutic effects of a taurine-magnesium coordination compound on experimental models of type 2 short QT syndrome

• 来源期刊: 中国药理学报（英文版）
• 关键词: short QT syndrome taurine-magnesium coordination compound pinacidil trapidil Langendorff guinea pig-perfused hearts ventricular myocytes IKs refractory period
• 年，卷（期）: 2018,（3）
• 页码范围: 382-392
• 页数: 11页
• 语种: 英文
• DOI: 10.1038/aps.2017.86

摘要

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.(NH2CH2CH2S03)2 · H20,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＜O.05 vs control).Subsequently,perfusion of TMCC (1-4 mmol/L) dose-dependently increased the QT interval and QTpeak (P＜O.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 ceils 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.