Figure 4. Unconstrained five-state... | Rockefeller University Press

Figure 4.

Unconstrained five-state gating polarity model. (A) Gating scheme of the five-state gating polarity model. Voltage-dependent transition steps, K1 and K2, and voltage-independent transition steps, K3 and K4, are all freely floating parameters. C is the closed state, and O is the open state of the pore. V is the state of the voltage sensor, where VR is at rest. Subscripts H and D for all O and V states indicate states upon membrane hyperpolarization and upon membrane depolarization, respectively. Equations for calculating PO−V plots are described in Materials and methods. Fitting of the PO−V plots to data using the gating scheme are shown as a solid black line in figure panels (B–I). Parameter values used for these fittings are reported in Table S1. PO−V scatter plot data in B and C are adapted from Tristani-Firouzi et al. (2002), and normalized again such that the maximum PO is normalized to 1 (i.e., relative current/maximum relative current). PO−V scatter plot data in D–I are adapted from Lin et al. (2024). (B–I)PO−V scatter plot data of D540K-Q664A hERG (upward-pointing triangle ▲), D540K-L666A hERG (square ■), HHHEH (diamond ♦), HHHEH2 (downward-pointing triangle ▼), HHHES (asterisk *), HHHER (right-pointing triangle ►), HHHEK (pentagram ★), and HHHEA (left-pointing triangle ◄).

Unconstrained five-state gating polarity model. (A) Gating scheme of the five-state gating polarity model. Voltage-dependent transition steps, K₁ and K₂, and voltage-independent transition steps, K₃ and K₄, are all freely floating parameters. C is the closed state, and O is the open state of the pore. V is the state of the voltage sensor, where V_R is at rest. Subscripts H and D for all O and V states indicate states upon membrane hyperpolarization and upon membrane depolarization, respectively. Equations for calculating P_O−V plots are described in Materials and methods. Fitting of the P_O−V plots to data using the gating scheme are shown as a solid black line in figure panels (B–I). Parameter values used for these fittings are reported in Table S1. P_O−V scatter plot data in B and C are adapted from Tristani-Firouzi et al. (2002), and normalized again such that the maximum P_O is normalized to 1 (i.e., relative current/maximum relative current). P_O−V scatter plot data in D–I are adapted from Lin et al. (2024). (B–I)P_O−V scatter plot data of D540K-Q664A hERG (upward-pointing triangle ▲), D540K-L666A hERG (square ■), HHHEH (diamond ♦), HHHEH₂ (downward-pointing triangle ▼), HHHES (asterisk *), HHHER (right-pointing triangle ►), HHHEK (pentagram ★), and HHHEA (left-pointing triangle ◄).