1. Schematics of GABAA receptor structure and function.
Schematics of GABAA receptor structure and function. A, topography of a GABAA receptor subunit partially embedded in the lipid bilayer. 1, N-terminal extracellular domain responsible for transmitter and ligand binding and coupling of the binding sites with ion channel. This part is also important for the allosteric effects and for the assembly of various receptor subunits into functional receptors. 2, four transmembrane regions forming the anion channel are responsible for binding of hydrophobic ligands, ion selectivity, and channel binding sites. 3, intracellular loop between transmembrane helices 3 and 4 forms the motif for regulatory phosphorylation sites and for the intracellular factors anchoring the receptors in appropriate locations (e.g., on the postsynaptic thickening) using interactions with auxiliary and cell structural proteins. B, hypothetical binding sites for GABA and allosteric modulators such as benzodiazepine ligands and a domain essential for the functions of various ligands such as etomidate, loreclezole, and methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate in a pentameric receptor complex. C, allosteric activation of GABAA receptor may increase the peak height (amplitude) of the response and/or prolong the response as compared with the response by GABA alone.
Mikko Uusi-Oukari, and Esa R. Korpi Pharmacol Rev 2010;62:97-135
© 2010 by The American Society for Pharmacology and Experimental Therapeutics