The pharmacology of extrasynaptic GABAA receptors

Abstract

The different subunits that make up the family of GABAA receptor subtypes have unique distributions within the brain and nervous system. Their localization at the neuronal level is in many cases not necessarily associated with synaptic densities, and this has led to the hypothesis that extrasynaptic receptors perform a unique function in controlling excitability. In most cases, the subunits that make up extrasynaptic receptors are different to those on synaptic membranes and hence have their own unique pharmacological profile, both in respect to agonists and allosteric modulators. Here I will review the different receptor subtypes that have been classified as extrasynaptic, as well as those that may serve both roles depending on their location, with a view to illustrating their pharmacological properties, and their impact on neuronal function. The identification of functional differences and allosteric sites for specific modulation of these receptors offers an opportunity to gain more knowledge of the role of receptor subtypes and the potential to develop novel therapeutic agents that should impact a number of psychiatric and neurological disorders where these receptors are implicated.