Fractional availability predictions for various models favor the idea that block of closed channels depends on voltage sensor movement. (A) Currents were simulated (10-state activation model) with the indicated voltage protocol (top left) for nominal 4 µM Ca²⁺ in the absence of blocker. Conditioning voltages were stepped in 20-mV increments, although for display purposes, only 40-mV increments are shown. (B) Currents were simulated with Scheme 1a, the open-channel block model. Red highlights traces (and voltage in red) in which the available fraction of current is ∼0.5. Half-availability occurs near +80 mV, and at voltages negative to +40 mV, there is no additional increase in current availability. (C) Currents were simulated for Scheme 2a. No saturation in fractional availability is observed down through −300 mV. (D) Currents simulated with Scheme 2b exhibit saturation in fractional availability with half-availability around 60–80 mV. (E) Currents simulated with Scheme 3a showed half-availability near +20 mV with clear saturation. (F) Currents simulated with Scheme 3b showed half-availability near +40 mV with clear saturation. (G) The activation GV for 4 µM Ca²⁺ (filled black circles) is plotted along with normalized fractional availability curves for the peak transient currents for different schemes, as labeled. The voltage dependency of availability for Schemes 1a (red squares) and 2b (blue circles) yield values comparable in magnitude to that of activation (z of ∼0.9 e). For Scheme 2a (red circles), the voltage dependence mirrors that of channel block (z of ∼0.2 e). For Schemes 3a (red diamonds) and 3b (blue diamonds), the magnitude of the voltage dependence is less than that predicted for open-channel block, characteristic of bbTBA of Slo1 current.