Models in which block is coupled to voltage sensor movement can account for differential ability of OB and CB–OB models to fit data at low and high Ca2+. (A) GV curves were generated with Scheme 1a, both with 4 µM Ca2+ (left) and 300 µM Ca2+ (middle). Simulations were done with nominal blocker concentrations of 0.14-, 0.57-, and 2.86-fold the effective Kb. Blue lines correspond to the best fit of a strictly open-channel block model (Eq. 8 with W = 100,000), and red lines correspond to the best fit of a completely state-independent CB–OB model (Eq. 8 with W = 1). On the right, the difference between OB–CB (Eq. 8 with W = 1) summed residuals measured for all [bbTBA] at each voltage and the OB summed residuals (W = 100,000) is plotted as a function of voltage. Points on the upper half of such plots indicate that the fit of the OB model (W = 100,000) yielded larger deviations than the W = 1 assumption. In this case, W = 1 yielded poorer fits both at 4 (filled circles) and 300 µM (open circles). (B) GV curves were generated from currents simulated using Scheme 2a (Kbo = Kbc and zo = zc). In this case, the W = 1 assumption fits the GV curves better at both 4 and 300 µM. (C) GV curves were generated with Scheme 2b (zc = 0 e) and fit as above. Again, the CB–OB equation provides a better fit both at 4 and 300 µM Ca2+. (D) GV curves were generated with Scheme 3a (Kbo = Kbc and zo = zc) and fit as above. The right-hand panel indicates that the GV curves at 4 µM were somewhat better fit with the CB–OB model, whereas at 300 µM, the standard OB model provided a better fit. Similar results were obtained with Scheme 3b (zc = 0 e).