Proarrhythmia in KCNJ2 E299V-linked Short QT Syndrome: A Simulation Study

Short QT syndrome (SQTS) is a clinical disorder associated with cardiac arrhythmias and sudden cardiac death (SCD). Short QT syndrome variant 3 (SQT3) has been linked to the D172N or E299V gain-in-function mutation to Kir2.1, which preferentially increases outward current through channels responsible for inward rectifier K+ current (I_{K1}). There is a novel blocker of Kir2.1, Styrax, which is a kind of natural compound selected from traditional Chinese medicine. In this study, the ten Tusscher et al model of ventricular action potential was used to investigate the potential effects of Styrax on the short QT syndrome associated with the Kir2.1 D172N mutation and E299V mutation. Our data showed that Styrax can prolong the action potential (AP) and QT interval on the ECG under the condition of SQT3 associated with D172N and E299V mutations. We suggested that Styrax may be a potential drug for the treatment of SQT3.