Optimized voltage clamp (VC) protocol correctly identifies IKr as a target of cisapride, quinidine and quinine. (a) Representative cell shows the effect of quinine on the current response during the segment of the VC protocol designed to isolate IKr. The black trace is pre‐drug, and the red trace is post‐drug. (b) The current trace during the segment meant to isolate IKr (shaded grey in panel a). (c) Cells treated with cisapride (C), quinidine (Qd) and quinine (Qn) showed a decrease in total current during the VC segment designed to isolate IKr. At the concentrations used in this experiment, cisapride, quinidine and quinine should block 95%, 89% and 72% of IKr, respectively. *P< 0.05, significantly different as indicated. (d–f) Functional t tests show a significant difference in the average change in current during the IKr‐isolating segment when comparing cells treated with DMSO to cells treated with cisapride (d), quinidine (e) and quinine (f). Verapamil was excluded because there was no significant difference during this segment of the protocol.