Simulation of the Undiseased Human Cardiac Ventricular Action Potential: Model Formulation and Experimental Validation
Figure 16
Major causes of steady state APD rate dependence and S1S2 APD restitution.
A) APD rate dependence in control (solid black), and with [Na+]i and [Na+]ss clamped to slow rate (solid gray) or fast rate (dashed black) values. When late INa (dashed gray) or both late INa and ICaL inactivation gates were reset to their slow rate values (dash-dot-dot gray) in addition to [Na+]i and [Na+]ss slow rate clamp, APD lost almost all rate dependence. Note that slow rate [Na+]i and [Na+]ss clamp alone left residual APD rate dependence, especially at fast rates (CL = 300 to 700 ms, shaded box). B) APD rate dependence (control, solid black) was largely unaffected by resetting inactivation gates for late INa (dashed gray), ICaL (dash-dot-dot gray), or late INa and ICaL (solid gray) to their slow rate values (no [Na+]i and [Na+]ss clamping to slow rate values). C) [Na+]i and INaK increase with pacing rate under control conditions (left). When [Na+]i and [Na+]ss are clamped to slow rate values, INaK is small and rate independent (right). D) APD restitution in control (solid black), and when inactivation gates were reset to S1 values upon S2 delivery (late INa reset – dashed gray, ICaL reset – dash-dot-dot gray, late INa and ICaL reset – solid gray). Shown in dashed black is resetting late INa and ICaL inactivation to the DI = 5 ms value. E) [Na+]i and [Na+]ss clamp to S1 values (dashed gray) did not affect APD restitution (control, solid black).