Extrasynaptic GABA(A) Receptors: Form, Pharmacology, and Function

Delia Belelli, Neil Harrison, Jamie Maguire, Robert L. Macdonald, Matthew C. Walker, David W. Cope

    Research output: Contribution to journalReview articlepeer-review

    296 Citations (Scopus)

    Abstract

    GABA is the principal inhibitory neurotransmitter in the CNS and acts via GABA(A) and GABA(B) receptors. Recently, a novel form of GABA(A) receptor-mediated inhibition, termed "tonic" inhibition, has been described. Whereas synaptic GABA(A) receptors underlie classical "phasic" GABA(A) receptor-mediated inhibition (inhibitory postsynaptic currents), tonic GABA(A) receptor-mediated inhibition results from the activation of extrasynaptic receptors by low concentrations of ambient GABA. Extrasynaptic GABA(A) receptors are composed of receptor subunits that convey biophysical properties ideally suited to the generation of persistent inhibition and are pharmacologically and functionally distinct from their synaptic counterparts. This mini-symposium review highlights ongoing work examining the properties of recombinant and native extrasynaptic GABA(A) receptors and their preferential targeting by endogenous and clinically relevant agents. In addition, it emphasizes the important role of extrasynaptic GABA(A) receptors in GABAergic inhibition throughout the CNS and identifies them as a major player in both physiological and pathophysiological processes.

    Original languageEnglish
    Pages (from-to)12757-12763
    Number of pages7
    JournalJournal of Neuroscience
    Volume29
    Issue number41
    DOIs
    Publication statusPublished - 14 Oct 2009

    Keywords

    • CEREBELLAR GRANULE CELLS
    • AMINOBUTYRIC ACID(A) RECEPTOR
    • TONIC GABAERGIC INHIBITION
    • RAT SOMATOSENSORY CORTEX
    • TEMPORAL-LOBE EPILEPSY
    • THALAMIC RELAY NEURONS
    • DELTA-SUBUNIT
    • NEUROSTEROID MODULATION
    • DENTATE GYRUS
    • NEUROACTIVE STEROIDS

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