The human ether-a-go-go-related gene (hERG) encodes the rapidly activating, 
delayed rectifier potassium channel (IKr) important for cardiac repolarization. 
Dysfunction of the hERG channel can cause Long QT Syndrome (LQTS). A wide 
variety of structurally diverse therapeutic compounds reduce the hERG current by 
acute direct inhibition of the hERG current or/and selective disruption of hERG 
protein expression. Arsenic trioxide (As(2)O(3)), which is used to treat acute 
promyelocytic leukemia, can cause LQTS type 2 (LQT2) by reducing the hERG 
current through the diversion of hERG trafficking to the cytoplasmic membrane. 
This cardiotoxicity limits its clinical applications. Our aim was to develop 
cardioprotective agents to decrease As(2)O(3)-induced cardiotoxicity. We 
reported that superfusion of hERG-expressing HEK293 (hERG-HEK) cells with 
matrine (1, 10 μM) increased the hERG current by promoting hERG channel 
activation. Long-term treatment with 1 μM matrine or oxymatrine increased 
expression of the hERG protein and rescued the hERG surface expression disrupted 
by As(2)O(3). In addition, Matrine and oxymatrine significantly shortened action 
potential duration prolonged by As(2)O(3) in guinea pig ventricular myocytes. 
These results were ascribed to the up-regulation of hERG at both mRNA and 
protein levels via an increase in the expression of transcription factor Sp1, an 
established transactivator of the hERG gene. Therefore, matrine and oxymatrine 
may have the potential to cure LQT2 as a potassium channel activator by 
promoting hERG channel activation and increasing hERG channel expression.