Forward–reverse activation model (Model FR). (A) Gating scheme for Model FR. Four identical resting voltage sensors independently activate with forward rate α and reverse rate β. Pore opening is modeled as a voltage-independent concerted event with rate kopen and reverse rate kclose. Rates susceptible to GxTx are red. (B) Simulated Popen from Model FR under control conditions. Light gray, 60 mV; dark gray, 90 mV; black, 120 mV. Dotted lines show fits of Eq. 3. τ60mV = 6.68 ± 0.01 ms, σ60mV = 1.602 ± 0.004; τ90mV = 6.413 ± 0.008 ms, σ90mV = 1.325 ± 0.002; τ120mV = 5.729 ± 0.004 ms, σ120mV = 1.141 ± 0.001. (C) Simulated Popen from Model FR with GxTx. Light pink, 60 mV; red, 90 mV; dark red, 120 mV. Dotted lines show fits of Eq. 3. τ60mV = 18.147 ± 0.008 ms, σ60mV =3.248 ± 0.003; τ90mV = 11.23 ± 0.01 ms, σ90mV = 2.508 ± 0.005; τ120mV = 9.28 ± 0.01 ms, σ120mV = 1.941 ± 0.004. (D) Comparison of the reciprocals of rates α and β to τON from Kv2.1 control gating currents. Hollow circles, mean Kv2.1 τON from Fig. 8 E; filled circles, α−1 from model; filled triangles, β−1 from model. Solid lines, fits of Eq. 8: zα = 0.65 ± 0.05 e0, α−10mV = 4.2 ± 0.3 ms; zβ = 0.17 ± 0.04 e0, β−10mV = 9 ± 1 ms. (E) Comparison of the reciprocals of rates α and β to τON from Kv2.1 gating currents in 1 µM GxTx. Hollow circles, mean Kv2.1 τON with 1 µM GxTx from Fig. 8 E; filled circles, α−1 from model; filled triangles, β−1 from model. Solid lines, fits of Eq. 8: zα = 0.73 ± 0.03 e0, α0mV−1 = 60 ± 7 ms; zβ = 0.50 ± 0.04 e0, β0mV−1 = 97 ± 15 ms.