SPD³⁺ and SPM⁴⁺ blockade described with Scheme 2 . (A) Fractional MthK current over a range of [SPD³⁺] with Scheme 2 predictions superimposed. Scheme 2 predicts that depolarization drives the channel toward a receptive open state (O’) with enhanced blocker affinity, accounting well for the experimental data. Fit parameters for individual experiments are provided in Table 3. (B) Fractional MthK current over a range of [SPM⁴⁺] with Scheme 2 predictions superimposed. Scheme 2 accounts for the major features of SPM⁴⁺ blockade over a 1,000-fold range of [SPM⁴⁺]. Fit parameters for individual experiments are provided in Table 4.