Figure 9.

Separation of charge systems: Q₁ and Q₂ can be represented by a four-state model. (A) Four-state model used to simulate the two charge components observed in hERG gating currents recorded from mammalian cells. Q₁ was modeled based on the isolated Q₁-V_off relation (z = 1.60; Fig. 5 A). Gating currents corresponding to Q₁ charge movements were well represented by a two-state, voltage-dependent transition with forward and backward transitions of equal voltage dependence (z = 0.8). The determination of Q₂ charge movement was based upon the charge distribution left after subtraction of the charge movements from the Q_total (Fig. 5 B). The total equivalent charge for Q₂ movement determined from the Boltzmann fit was similar to that of Q₁, with z = 1.3 (Fig. 5 D). Q₂ was modeled as two transitions, each with a total equivalent charge movement of z = 2. (B) Q₁ simulations. Voltage-independent rate constants were adjusted by fitting the simulated gating currents to the Q₁-V_off and V_1/2 in Fig. 5 and had values of k_{0–1(0 mV)} = 1,915 s⁻¹ and k_{1–0(0 mV)} = 58 s⁻¹. Clamp protocols are as in Fig. 5 for repolarization steps to −30, −60, and −90 mV. Simulated currents are shown below, and the Q₁-V_off relations are shown at the bottom. (C) Q₂ simulation had voltage-independent rate constants of k_{1–2(0 mV)} = 195 s⁻¹, k_{2–1(0 mV)} = 1.8 s⁻¹, k_{2–3(0 mV)} = 88 s⁻¹, and k_{3–2(0 mV)} = 7.9 s⁻¹. (D) Q_total simulation with Q₁ and Q₂ components displayed as in Fig. 6 B.