Figure 1.

(a) Predicted open fraction ƒ_O(t) for a 1.5 s pulse of anesthetic for a wide range of concentrations: c_an = 0.5 mM (black solid line), 1.0 mM (black dashed line), 1.5 mM (black dotted line), 2.5 mM (black dot-dashed line), 3.0 mM (blue solid line), 5.0 mM (blue dashed line), 7.5 mM (blue dotted line), and 15.0 mM (blue dot-dashed line). (b) Equilibrium conformational distribution as a function of anesthetic concentration c_an: ƒ_O,eq (solid line), ƒ_R,eq (dashed line), and ƒ_D,eq (dotted line). Note the different scales for ƒ_O,eq (right ordinate) and for ƒ_R,eq and ƒ_D,eq (left ordinate). The shape of the distribution results from the increase in G(R) and the decrease in G(D) relative to G(O) upon bilayer adsorption of anesthetic. A key feature is the prediction of a very steep decrease in ƒ_O,eq after its maximum (i.e., for c_an > c_an,max ≈ 2 mM) as observed experimentally (9), which is inconsistent with a mechanism based on anesthetic binding to a channel-blocking site. To see this figure in color, go online.