The reverse stimulation-rate dependence of Y1795C on Isus and APD. (a) The 19th and 20th APs from virtual cells containing WT (left) and Y1795C (right) channels with corresponding INa (at high gain, bottom) (see Methods). The Y1795C mutation clearly results in larger Isus (arrow) compared with WT that becomes progressively larger as the stimulation rate is slowed, as indicated by the APs shown in (b) (stimulation rate, 1,200 milliseconds). (c) Computed APD for cells expressing WT and Y1795C channels plotted against simulated stimulation cycle length (CL). As the cycle length becomes progressively longer (simulating slowing of heart rate), the WT and Y1795C adaptation curves diverge, indicating that the Y1795C mutation exerts its deleterious effects preferentially at slow stimulation rates.