Fig. 3: General scheme for the simulation of desensitization: an asymmetric non-concerted model.
From: The desensitization pathway of GABAA receptors, one subunit at a time
The first part in the kinetic scheme is the binding of the agonist A to the resting state R, which favors the opening of the channel (AO state) with a gating efficacy E = β/α. Of note, unliganded openings do exist but are not taken into account for our kinetic modeling as they barely contribute to the electrophysiological response (see main text). We also only include one binding event, even though α1β2γ2 GABAARs contain two binding sites whose occupation is required for substantial activation. Upon channel opening, the receptor can then transit from a fully activated AO state to states where only one subunit enters its desensitized conformation (AD3, AD4, and AD5). From these states, a second subunit can also desensitize, before the final step leading to the state in which all subunits are desensitized.
