Fig. 8.

Linear I_f current–voltage relationships are due to slow activation and deactivation rates. (A) Simulated current–voltage relationships in response to a representative sinoatrial AP recorded in 1 nM isoproterenol using the base 1 nM isoproterenol model of I_f (black), a model of HCN1 (light gray) (50), or a model of HCN2 gating (dark gray) (51). Black arrows indicate the progression of the current–voltage relationship over time. (A, Inset): Simulated currents during single sinoatrial APs using the base 1 nM isoproterenol model of I_f, the HCN1 model, or the HCN2 model. (B–D) Current–voltage relationships of simulated I_f in response to prerecorded sinoatrial APs using the base 1 nM isoproterenol model (black), the 1 µM isoproterenol model (red), or the 1 nM model with altered activation voltage dependence (B), forward (α) rates of activation (C), or reverse (β) rates of activation (D). Activation voltage dependence (V_1/2) was shifted by −5 mV (blue) or +5 mV (green). The α- and β-rates of the activation gate were slowed by 50× (blue) or sped up 50× (green). (B–D, Insets) Simulated I_f during single sinoatrial APs using the base 1 M isoproterenol model, the 1 µM isoproterenol model, or models with altered activation voltage dependence (B, Inset), α-rates (C, Inset), or β-rates (D, Inset). Color schemes in B–D, Insets are the same as the main panels. Horizontal lines indicate zero current.