Figure 3.

(A) Kinetic model of hERG currents before and after PIP₂ application. Activation and inactivation are modeled as uncoupled processes. The channel is open when it is in the O and NI states at the same time. To focus on activation properties, transition rates regarding inactivation (α_I, β_I) are determined before and after PIP₂ addition from a concomitant fit of voltage-dependent inactivation rates and recovery-from-inactivation kinetics (Fig. S2). (B) Simulated and recorded hERG currents for the three protocols before and after PIP₂ application. The transition rates and biophysical parameters determined from these simulations are shown in Table S1. Optimization of the late voltage-independent transitions (α_P, β_P), supposed to be related to the pore domain, leads to a reasonable fit of the PIP₂ effect that is as good as the fit obtained by optimizing all transition rates. Conversely, optimization of early voltage-dependent transition rates (α_VS1, β_VS1, α_VS2, β_VS2), supposed to be mainly related to the voltage sensing of hERG, leads to a poor fit of the PIP₂ effect.