Figure 12.

Distinguishing between Scheme IIA (H⁺ binding inhibits Ca²⁺ binding) and Scheme IIB (H⁺ binding inhibits gating). (A) Scheme IIA (black dashed lines) predicts that at low to nominally 0 Ca²⁺, the minimum Po does not change with pH, whereas Scheme IIB (red dashed lines) predicts that the minimum Po decreases by >10-fold per 0.5-unit decrease in pH (i.e., an approximate threefold increase in [H⁺]). (B) Po measured at nominally 0 Ca²⁺ plotted as a function of pH (filled circles), superimposed on the predicted Po at nominally 0 Ca²⁺ for Scheme IIA (black dashed line) and Scheme IIB (red dashed line). These data illustrate that Scheme IIA, in which H⁺ binding inhibits Ca²⁺ binding with no direct coupling between H⁺ binding and channel gating, is consistent with the experimental data.