Fig. 11.

Illustration of the effects of partial block of one or two K⁺ channels resulting in “double-hit” pharmacological inhibition. The rate dependence of the action potential (AP) duration at 90% repolarization (APD₉₀) after a simulated 50% block of ultrarapid delayed rectifier K⁺ current (I_Kur; red) or both Ca²⁺-independent transient outward K⁺ current (I_to) and I_Kur (blue) in baseline model conditions and in the model including partial substitution of Kv1.4 for Kv4.3 was assessed. A: simulated rate dependence of APD₉₀ in response to partial block of both I_to and I_Kur using the baseline model under sinus rhythm (SR; Aa) and atrial fibrillation (AF; Ab) conditions. B: simulated rate dependence of APD₉₀ after partial (50%) block of both I_to and I_Kur in the modified human atrial AP model that includes partial substitution of Kv1.4 for Kv4.3. Results are shown for both SR (Ba) and AF (Bb) conditions.