Fig. 3.
Experimentally measured and model predicted effect of GS-458967 on INa in rabbit ventricle. (A) Optimized model generated concentration-dependent data for GS-458967 on late Na current compared to two separate sets of experimental data - Blue asterisks indicate experimental data set #1 (n = 4) [9], and red circles are from experimental data set #2 (For 0 μM and 0.03 μM, n = 3. For 0.1 μM and 0.3 μM, n = 4. For 1 μM, n = 6. For 3 μM, n = 2). The effect of high concentration GS-458967 on peak INa is indicated for experiments (blue square), and simulated INa peak (black triangle). (B) Behavior of a myocyte ‘population’ was simulated by randomly varying the amplitude of maximal conductances for INa, ICaL, IKs, IKr, IK1, Ito, INaK, INaCa (to within 10% of their nominal values in the rabbit ventricular myocyte model). This approach allowed for efficient analysis of 100 distinct cell action potentials. APD90 was calculated at 1 Hz for each case. These simulated myocyte properties were compared to experimental data set #1 (blue asterisks) and experimental data set #2 (red circles).