Abstract: Occurrence of severe life-threatening arrhythmias is based on ion channelopathies in the sarcolemma or sarcoplasmic reticulum of myocardium.It has not been successful in research and development of antiarrhythmic agents which failed to suppress life-threatening tachyarrhythmias in the two famous clinical trials (CAST&SWORD) , attributed to lack of understanding of the channelopathy in myocardium.Patients with the LQTS(Long QT syndrome) caused by mutations in the hERG,KvLQT1 and SCN5A or the SQTS (short QT syndrome) by gain-of-function mutations in hERG and KvLQT1 or CPVT caused by mutation of RyR2 gene in sarcoplasmic reticulum, are at risk to developlife-threatening arrhythmias.Cardiomyopathy induced by L-thyroxin medication shares some resemblance with the above gene mutations and manifests varied length of APD.It provides an ideal animal model to investigate the mechanism underlying cardiac arrhythmias and evaluate activity of antiarrhythmic agents.CPU86017, an agent to block multiple ion channels,and CPU0213, a novel endothelin receptor antagonist,are under investigated and possess a promising effect to suppress cardiac arrhythmias by correcting the channelopathy in myocardium.

Key words: cardiac arrhythmias, antiarrhythmic agents, ion channels, channelopathy