Allosteric factor, n, of the inverted coupling model modulates gating polarity. (A) Gating scheme of the inverted coupling model. C and O are when the pore is closed and opened, respectively. VD and VH are the voltage sensor upon membrane depolarization and upon membrane hyperpolarization, respectively. K1 is a voltage-dependent equilibrium state constant for movement of the voltage sensor. K2 is voltage-independent for opening and closure of the pore. n is the allosteric factor. Equations for calculating the PO−V curves are described in Materials and methods. (B) Family of PO−V plots based on the gating scheme in A. The = 1, q1 = −1, and K2 = 1 are the same for all except for n, which is varied as shown in the legend. (C)PO−V scatter plot of hEAG (adapted from Cowgill et al. [2019]). These data were fitted (dashed black line) with the following parameters: = 22.4, q1 = −1.46, and K2 = 143. n = 3.38 × 10−5. PO-V plots in blue correspond to varying values of n when n is <1. (D)PO−V scatter plot of mHCN1 (adapted from Cowgill et al. [2019]). These data were fitted (dashed black line) with the following parameters: = 1.13 × 10−4, q1 = −2.03, and K2 = 0.0139, n = 1,550. PO−V plots in red correspond to varying values of n when n is >1.