Figure 5.
Predicted effects of changes in the open-state affinity for the unlabeled ligand on equilibrium binding-competition concentration–response curves. Curves were calculated using the reaction scheme in Fig. 1 with a variable KDA,open value and the following fixed parameters: KC⇌O = 10−7; KDA,closed = 1 μM; and KDB,closed = KDB,open = 1 nM. Other details of the calculations and the display of the predictions are given in the legend to Fig. 2. (A) Calculated curves. (B) Half-competition concentration values. (C) Hill-coefficient values. The corresponding estimates ranged between unity and ∼4.2. In B and C, the liganded-gating equilibrium constants (Eq. 6) decrease from left to right. A vertical dashed line indicates where KDA,open = KDA,closed. Hence, to the right of this value, the unlabeled ligand is an inverse agonist, and to the left, an agonist.