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 GABAA 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 GABAA receptor, summarize analytical expressions for activation and interaction for drugs, and briefly review experimental results.
Footnotes
- Received July 25, 2018.
- Accepted October 12, 2018.
This work was supported by the National Institutes of Health National Institute of General Medical Sciences [Grant R01GM108580] and funds from the Taylor Family Institute for Innovative Psychiatric Research. No potential conflicts of interest relevant to this article are reported.
- Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics