Applying the Monod-Wyman-Changeux Allosteric Activation Model to Pseudo-Steady-State Responses from GABAA Receptors

Abstract

The Monod-Wyman-Changeux (MWC) cyclic model was described as a kinetic scheme to explain enzyme function and modulation more than 50 years ago and was proposed as a model for understanding the activation of transmitter-gated channels soon afterward. More recently, the MWC model has been used to describe the activation of the GABA_A receptor by the transmitter, GABA, and drugs that bind to separate sites on the receptor. It is most interesting that the MWC formalism can also describe the interactions among drugs that activate the receptor. In this review, we describe properties of the MWC model that have been explored experimentally using the GABA_A receptor, summarize analytical expressions for activation and interaction for drugs, and briefly review experimental results.