Induction of the substrate-exchange mode requires cooperative binding. (A) Simulated peak current recovery experiment using intracellular Na⁺ concentrations of 0 M or 140 mM using a cooperativity factor of 30. The time course of recovery after substrate application was modeled as the time course of return to ToClNa (Fig. 5 A). (B) Simulated peak current recovery experiment using intracellular Na⁺ concentrations of 0 M or 140 mM, but with a cooperativity factor of 1 (i.e., purely random order). The dashed curve reached steady state after 230 s (not depicted).