Current simulations with different blocking models. (A) Families of traces show control currents (no bbTBA) simulated with the indicated voltage protocol and either 4 µM Ca²⁺ (left) or 300 µM Ca²⁺ (right) using the 10-state activation model (Fig. S1 A). (B) Currents were simulated with classical open-state block in conjunction with the 10-state activation model (Scheme 1a). The slower onset of block in comparison to models with block of closed states reflects the coupling of inactivation to activation. (C) Traces show currents activated by the same conditions but with blockade defined by the full state–independent blocking model (Scheme 2a) with K_bo = K_bo and z_o = z_c. Note the prominent triphasic currents at 4 µM Ca²⁺. (D) Traces show currents simulated with Scheme 3a (block depends on activation of at least one voltage sensor) as well as prominent triphasic current relaxations at 4 µM.