Bipolar gating phenotype is described using the three-state gating polarity model. (A) Gating scheme of the three-state gating polarity model. C is when the channel is closed. O_H is channel opening upon membrane hyperpolarization, and O_D is channel opening upon depolarization. K₁ and K₂ are voltage-dependent equilibrium state constants. Equations for calculating P_O−V curves are described in Materials and methods. All plots were generated using the parameters q₁ = −2 and q₂ = 2. (B)P_O−V scatter plot of D540K-hERG mutant (adapted from Tristani-Firouzi et al. [2002]). These data were normalized again such that the maximum P_O is normalized to 1 (i.e., relative current/maximum relative current). The bipolar gating phenotype is observed when $K10$ = $K20$ = 0.025 (dashed black line). Fitting of these data can be approximated by setting $K10$ < $K20$ such that $K10$ = 0.0001 and $K20$ = 5 (solid black line). (C) Series of P_O−V plots show the result of $K10$ becoming increasingly smaller than $K20$ (solid lines with increasingly lighter shades of red), where $K20$ = 0.025 and $K10$ is equal to $K20$ multiplied by a varying factor (shown in figure legend). (D) Series of P_O−V plots show the result of $K20$ becoming increasingly smaller than $K10$ (solid lines with increasingly lighter shades of blue), where $K10$ = 0.025 and $K20$ is equal to $K10$ multiplied by a varying factor (shown in figure legend).