Figure 1. Fundamental mechanisms by which arousal and exercise triggers differentially affect LQT1 vs. LQT2.

The normal cardiac AP is shown in black in all panels, whereas APs in LQT1 or LQT2 are shown in red and green, respectively (baseline APs are shown as continuous lines in each panel). Dashed and dotted lines in middle and right panels indicate changes resulting respectively from arousal (adrenergic surge) and exercise (sustained increase in adrenergic tone). Since I_Kr is the predominant repolarizing current under normal conditions, APs are more prolonged in LQT2 at baseline. With sudden arousal stimuli, there is a transient surge of adrenergic tone, which increases I_CaL before any change in I_Ks. In LQT2, with major loss in repolarisation reserve due to loss of I_Kr, APs are strongly prolonged and EADs arise. In LQT1, intact I_Kr prevents excess AP prolongation. With exercise, sustained increases in adrenergic tone increase both I_CaL and I_Ks, producing little net change in AP duration when I_Ks is intact. However, when I_Ks is dysfunctional and cannot increase to compensate for I_CaL enhancement (LQT1), strong AP prolongation and EADs occur.