(-)-Epicatechin rescues the As₂ O₃ -induced HERG K⁺ channel deficiency possibly through upregulating transcription...

(-)-Epicatechin (EPI) has beneficial effects on the cardiovascular disease. The human ether-a-go-go-related gene (HERG) potassium channel is crucial for repolarization of cardiac action potential. Dysfunction of the HERG channel can cause long QT syndrome type 2 (LQT2). Arsenic trioxide (As₂ O₃ ) has shown efficacy in the treatment of acute promyelocytic leukemia. However, As₂ O₃ can induce the deficiency of HERG channel and cause LQT2. In this study, we examined whether EPI could rescue the As₂ O₃ -induced HERG channel deficiency. We found that 3 μM EPI obviously increased protein expression and current of HERG channel. EPI was able to recover the protein expression and current of HERG channel disrupted by As₂ O₃ . EPI was able to increase the expression of SP1 protein and recover the expression of SP1 protein disrupted by As₂ O₃ . In addition, EPI significantly shortened action potential duration prolonged by As₂ O₃ . Our data suggest that EPI rescues As₂ O₃ -induced HERG channel deficiency through upregulating SP1 expression.