SPD³⁺ blockade described with an alternative three-state model (Scheme 4 ). Mean fractional MthK current (I/I₀) over a range of [SPD³⁺], with Scheme 4 predictions superimposed (solid red curves). (A) Scheme 4 (left), with equations describing fractional current (right). (B) Mean fractional MthK current (I/I₀) over a range of [SPD³⁺] as indicated, with Scheme 4 predictions superimposed (solid red curves). The best fit with this model (χ² = 35.4) predicts that MthK currents will ultimately reach 100% blockade with very strong depolarization, although the apparent voltage dependence of blockade is less steep than that of Scheme 1. (C) An alternative fit representing a local minimum (χ² = 97.6) predicts that MthK currents can increase with very strong depolarization.