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

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.

• Authors: Meng-Yao An, Kai Sun, Yan Li, Ying-Ying Pan, Yong-Qiang Yin, Yi Kang, Tao Sun, Hong Wu, Wei-Zhen Gao, Jian-Shi Lou
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 39 Issue 3 Pg. 382-392 (Mar 2018) ISSN: 1745-7254 [Electronic] United States
• PMID: 29072257 (Publication Type: Journal Article)

Chemical References

• Coordination Complexes
• Taurine
• Pinacidil
• Trapidil
• Magnesium

Topics

• Action Potentials (drug effects)
• Animals
• Arrhythmias, Cardiac (chemically induced, prevention & control)
• Cells, Cultured
• Coordination Complexes (pharmacology)
• Guinea Pigs
• Heart Conduction System (abnormalities)
• Heart Defects, Congenital (chemically induced, prevention & control)
• Humans
• Magnesium (chemistry, pharmacology)
• Models, Theoretical
• Myocytes, Cardiac (physiology)
• Pinacidil (antagonists & inhibitors, pharmacology)
• Taurine (chemistry, pharmacology)
• Trapidil (antagonists & inhibitors, pharmacology)