Allosteric models recapitulate the various voltage- and ligand-dependent properties of WT HCN2, the HCN2/1 chimera, and the HCN1_minimal mutant. (A) Schematic representation of the various allosteric elements and interactions implemented in Scheme 4. Binary elements for the pore (P), voltage sensors (VS), linker (L), and binding domain (CNBD) are characterized by equilibrium constants (K_eq) between two states. Coupling factors (Θ) characterize the interactions between elements. All the parameters, except those marked in red, were kept constant to fit the kinetic and steady-state data for WT HCN2, HCN2/1, and the HCN1_minimal mutant. (B–D) Model fits (red) and experimental data (black) of current traces in response to voltage steps in the presence and absence of cAMP. Reference data for the apparent P_o-voltage curves (right) were obtained from the steady-state conductances at the end of each pulse and are compared with the maximum probability of the open state calculated for the model. Refer to Tables S2, S3, and S4 for a complete list of all parameters.