Fig. 5.

A cartoon schematic illustrating the salient features of channel activation and desensitization and the two-gate mechanism. The unliganded shut (S) channel binds two molecules of ligand (orange), which initially induce a structural reorientation of the extracellular domain (dark grey) producing a liganded shut state (A ₂ S). This is followed by a structural change in the transmembrane domain (red), which disrupts the activation gate to produce an open channel (A ₂ O). The continued presence of ligand elicits a further structural change in the extracellular domain (light brown) and transmembrane domain (dark brown) that occludes the pore with a second desensitization gate