Looking for GABA in all the wrong places: the relevance of extrasynaptic GABA(A) receptors to epilepsy.

It comes as no surprise that a high concentration of gamma-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 delta 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 delta subunit to epilepsy, providing a missing link between tonic inhibition and control of brain excitability.