FIG. 5.

Effect of the state-dependence and kinetics of drug binding on APD₉₀. APD₉₀ was determined for open (1-Hz [a] and 3-Hz [c] pacing rates) and open and inactivated (1-Hz [e] and 3-Hz [g] pacing rates) state blockers given nine different rates of binding kinetics between 0.01 and 100 s⁻¹ using half-logarithmic increments, whereby k_off = k_on and K_d = 1 μM. These simulations were also run in drug-free conditions, given a 50% and 100% reduction in g_Kur (dashed lines in a, c, e, and g). Simulations were equilibrated for 300 beats at 1-Hz pacing or 900 beats at 3-Hz pacing using a [drug] equal to the IC₅₀ value. (b), (d), (f), and (h) show the closed, open, inactivated, and drug-bound (d_B, i.e., Od or Od + Id) state occupancies during an AP for three different drug-binding kinetics (k_off = k_on = 0.01, 3, and 100 s⁻¹).