Figure 1.

Uncertainty in bepridil-hERG binding kinetics. (A) The joint probability distribution of K_max (maximum drug effect at saturating concentrations), K_u (rate of drug unbinding), n (Hill coefficient of drug binding), EC₅₀ⁿ (nth power of the half-maximal drug concentration), and V_halftrap (drug trapping potential) was estimated by bootstrapping. Plots on the diagonal show the marginal histograms of each parameter (log-transformed in some cases). Plots below the diagonal show pairwise scatter plots of the fitted parameters for 2,000 bootstrap samples. (B) Kinetics of hERG block during 10 sweeps of a modified Milnes voltage-clamp protocol (Milnes et al., 2010; Li et al., 2017). Shaded areas show the range of block produced by the parameters from (A). Lines show the experimental results used to fit the data (down-sampled 5× for clarity).