AP and electrocardiographic waveforms. Vm and IKs currents are color coded. Currents, with the exception of L51H, are in the presence of KCNE1. (A) Schematic of canine AP model (from Decker et al., 2009). (B) APs (thick lines) and currents (thin lines). Currents and APs are color coded: red, WT IKs; blue, E160K; orange, L51H. The mutations prolong the AP duration to varying degrees, depending on the severity of the mutation (degree of charge replacement at position 160 on S2). (C) Simulated pseudo ECGs. All mutations prolong the QT interval, the electrocardiographic marker of the long QT syndrome. For the naturally occurring mutations, the LQT1 mutation E160K (replacement of negative by positive charge) shows the greatest QT interval prolongation compared with mild prolongation by the LQT5 mutation L51H, consistent with the clinical phenotypes. Modified from Silva et al. (2009).
