The GABAA receptor and benzodiazepine acceptor site

Abstract

The GABAA receptor is a member of the ion channel receptor family. It is sensitive to muscimol (agonist) as well as bicuculline and picrotoxin (antagonists). The binding of GABA on its recognition site causes the opening of a chlorine (Cl-) channel, which, allowing the Cl-ions to pass, produces the hyperpolarization of the target cell. The GABAA receptor is a transmembrane glycoprotein composed of 4 subunits, alpha, beta, gamma and delta, currently recognized. It is sensitive to muscimol (agonist) as well as bicuculline and picrotoxin (antagonists). There are several types of GABAA receivers, different from each other by some of their subunits. There are currently 6 subtypes of alpha subunits, 3 subtypes of beta subunits, 3 subtypes of gamma subunits and 1 subtype of delta subunits. This entails not only a great heterogeneity of structure but also a pharmacological heterogeneity, the consequences of which are still poorly understood. The GABAA receptor has, besides the GABA receptor sites, a variety of other topographically distinct receptor sites capable of recognizing pharmacologically active substances, such as benzodiazepines (BZDs) -barbiturates -neurosteroids -convulsants -alcohol. These substances act in an allosteric manner with the GABA receptor sites and modulate the GABAA response.