Figure 1.

Connecting the VSD state to the cardiac action potential. A model of slow delayed rectifier K⁺ current (I_Ks) was built to explicitly represent the VSDs and to understand how their state affects action potential dynamics. This figure was adapted from (16). (A) Following previous work (15), a 16-state model was built on the assumption that each VSD can occupy three potential states, resting (R1), intermediate (R2), and active (A). When all four VSDs enter the active state, the channel is permitted to make a cooperative transition into the open state. The model is divided into two zones. Zone 1 contains channels where all four VSDs have already accomplished the R1 to R2 transition. Zone 2 contains channels that have yet to make the transition. (B) Inserting the model into the action potential demonstrates that the I_Ks current increases at rapid pacing rates, which causes shortening of the action-potential duration. This rate-dependent shortening of the action potential allows for ventricular filling during diastole. Examining VSD occupancy shows that at fast rates, channels reside in Zone 1, where they are ready to open, increasing I_Ks for the next action potential.