Looking for GABA in All the Wrong Places: The Relevance of Extrasynaptic GABAA Receptors to Epilepsy

Authors

  • George B. Richerson M.D., Ph.D.


  • Supported by NINDS NS43288 and the VAMC.

George B. Richerson, M.D., Ph.D., Departments of Neurology and Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, CT & Veteran's Affairs Medical Center, West Haven, CT; E-mail: george.richerson@yale.edu.

Abstract

Editor's note: Please see commentary by Mody pages 248–249 which highlights the same topic.

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 GABAA receptors also are far away from synapses. These extrasynaptic GABAA receptors are tonically activated by the low levels of GABA normally present in the extracellular space. Many of these extrasynaptic GABAA receptors contain the δ subunit. This subunit confers molecular properties on GABAA 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.

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