Figure 3. Migration of the Na⁺ ion across the receptor to the intracellular side.

(A–B) Z-coordinate of the Na⁺ ion in m2r under a hyperpolarised Vm of -250 mV (A) and -500 mV (B). Black and grey lines denote simulations with charged D69^2.50; purple, green and red lines display simulations with neutral D69^2.50. (C–D) Trajectories of the Na⁺ ion moving from the hydrophilic pocket, accessible from the extracellular space, into the intracellular bulk solution at -250 mV (C) and -500 mV (D). Three example trajectories are shown for each Vm; please see table S1 for a complete list. The color used to display the Na⁺ ion corresponds to the trajectories shown in panels A and B, respectively. Examples of the Y440^7.53 upward and downward conformations are shown in green. The pathways of the ion toward the intracellular side are almost indistinguishable from each other until the ion passes Y440^7.53. Thereafter, the pathways diverge to some degree due to the widened exit region to the cytoplasm.