Looking for GABA in all the Wrong Places: The Relevance of Extrasynaptic GABA A Receptors to Epilepsy

Abstract

It comes as no surprise that a high concentration of γ -aminobutyric acid (GABA) A receptors exists across the synapse from presynaptic terminals that contain GABA. Oddly, though, many GABA A receptors also are far away from synapses. These extrasynaptic GABA A receptors are tonically activated by the low levels of GABA normally present in the extracellular space. Many of these extrasynaptic GABA A receptors contain the δ subunit. This subunit confers molecular properties on GABA A receptors that are well suited for a function in tonic inhibition, with a high affinity for GABA and little desensitization to continuous activation. Recent data linked a genetic variant of the δ subunit to epilepsy, providing a missing link between tonic inhibition and control of brain excitability.