Long QT syndrome (LQTS) is a heart rhythm disorder that increases the risk of fatal cardiac arrhythmia known as Torsade de Pointes (TdP). One common cause of LQTS (type 2) is a mutation in HERG gene, which encodes the rapidly activating delayed rectifier potassium channel (IKr) and reduces channel activity by causing defective channel trafficking to the surface membrane. Previous studies in animals have shown that arsenic trioxide (As2O3) treatment can disrupt HERG channel trafficking and induce LQTS. In this study we report the ability of As2O3 to induce a LQT phenotype in commercially available human induced pluripotent stem cells (iPSC) cardiomyocytes. iPSC (obtained from Cellular Dynamics Incorporated), were maintained in culture for 10 days before exposing to 10 µM As2O3 in serum free medium for 1 or 24 hrs. The cells were then washed in serum free medium and exposed transiently to 3 µM Di-4-ANEPPS and left for 60-90mins before electrical recordings were made. The multi-well plate was placed on a stage incubator of an inverted microscope and the spontaneous electrical activity was recorded from the Di-4-ANEPPS fluorescence signal from areas of iPSCs in individual wells visualized using a 40x (NA0.6) objective. Fluoresence signals were digitized at 10kHz and the digital records subsequently analysed off-line. Under basal conditions, the spontaneous activity occurred every 1.98±0.54s (n=14) and the mean action potential duration at 75% repolarization (APD75) was 539±18ms. Treatment with As2O3 for 1 hr had no effect on the action potential duration (control vs. As2O3; 433±51 vs. 425±37), exposure for 22-24hrs prolonged APD75 significantly (P<0.05) to 601±21 ms (n=12) without any change in the rate of spontaneous activity (1.93±0.50s). Addition of the HERG channel inhibitor E4031 (30nM) increased APD75 in both groups (control: 1162±181ms and As2O3:1591±129ms). Early afterdepolarizations (EADs) occurred more frequently in the As2O3 group after treatment with E4031 (3 and 10nM) than in the corresponding control group. In conclusion, As2O3 treatment pronged APD in iPSCs. Treatment with a HERG channel blocker causes a further prolongation of APD and increased the incidence of arrhythmic events when compared to the control group. Thus As2O3 treatment was able to recapitulate the prolonged action potential duration and increased pro-arrhythmic sensitivity to HERG channel blockade associated with LQTS in human hearts.