hERG channels mediating the rapid delayed rectifier K+ current (IKr) are important for normal ventricular repolarization. In native cardiac tissues, hERG 1a subunit co-assembles with a subunit encoded by an alternate transcript, “ERG1b” which has a shorter N-terminus (1) and influences current kinetics (2). To date most pharmacological investigations of hERG sensitivity to drugs have been confined to hERG 1a. However, some studies suggest that hERG1b may confer altered pharmacological properties on hERG 1a+1b (2,3). Here, we aim to explore and characterise the differential sensitivity of hERG currents (IhERG) carried either by hERG1a, hERG1a+1b or 1b alone to cardiac and non cardiac drugs, under conventional voltage clamp. Recordings were made at 37°C from Human embryonic kidney (hEK) 293B cells either stably expressing hERG 1a channel or transiently transfected with hERG1a+ hERG1b or hERG 1b alone. Whole-cell recordings utilised a standard external Tyrode's solution and K+-based pipette solution. We found the anti-malarial agent chloroquine to inhibit hERG1a tail current at −40mV with an IC50 of 0.89 ± 0.06 μM (n=4-5 cells per concentration). Co-expression of hERG1a with hERG1b caused a shift in sensitivity with IhERG inhibited with an IC50 of 1.5 ± 0.06 μM (n= 5-7 cells per concentration). When IhERG was carried by hERG 1b alone, IC50 for IhERG inhibition was 1.3 ± 0.1 μM (n= 4-5 cells per concentration). Additional in vitro investigations of hERG cardiac and non cardiac drugs are ongoing to elucidate further the effect of the co-expression of hERG 1b subunit on IhERG drug sensitivity.This work was supported by the British Heart Foundation.1. Jones EM et al. (2004) J Biol Chem. 79(43):44690-42. Sale H et al. (2008) Circ res. 103(7):e81-953. Abi-Gerges N et al. (2011) Br J Pharmacol. 164(2b):419-32