Negative cooperativity between substrate and K⁺. (A) Simulation of radioligand binding at steady state. The simulations reproduce experimental data described in Bhat et al. (2017). The rates of imipramine binding were k_on, 5 × 10⁶ M⁻¹ s⁻¹; k_off, 0.015 s⁻¹. (B) Simulation of uptake inhibition using different negative cooperativity factors (ω values). The simulation using an ω value of 200 reproduces experimental data described in Bhat et al. (2017). (C) Simulated 5-HT–induced currents.