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GABA-Independent GABAA Receptor Openings Maintain Tonic Currents

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  • A. I. Wlodarczyk
  • S. Sylantyev
  • M. B. Herd
  • F. Kersante
  • J. J. Lambert
  • D. A. Rusakov
  • A. C. E. Linthorst
  • A. Semyanov
  • D. Belelli
  • I. Pavlov
  • M. C. Walker

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    Rights statement: Published in final edited form as: J Neurosci. 2013 February 27; 33(9): 3905–3914. doi: 10.1523/JNEUROSCI.4193-12.2013

    Accepted author manuscript, 2.21 MB, PDF document

Original languageEnglish
Pages (from-to)3905-3914
JournalJournal of Neuroscience
Volume33
Issue number9
DOIs
Publication statusPublished - 27 Feb 2013

Abstract

Activation of GABAA receptors (GABAARs) produces two forms of inhibition: ‘phasic’ inhibition generated by the rapid, transient activation of synaptic GABAARs by presynaptic GABA release, and tonic inhibition generated by the persistent activation of peri- or extrasynaptic GABAARs which can detect extracellular GABA. Such tonic GABAAR-mediated currents are particularly evident in dentate granule cells in which they play a major role in regulating cell excitability. Here we show that in rat dentate granule cells in ex-vivo hippocampal slices, tonic currents are predominantly generated by GABA-independent GABAA receptor openings. This tonic GABAAR conductance is resistant to the competitive GABAAR antagonist SR95531, which at high concentrations acts as a partial agonist, but can be blocked by an open channel blocker picrotoxin. When slices are perfused with 200 nM GABA, a concentration that is comparable to cerebrospinal fluid concentrations but is twice that measured by us in the hippocampus in vivo using zero-net-flux microdialysis, negligible GABA is detected by dentate granule cells. Spontaneously opening GABAARs, therefore, maintain dentate granule cell tonic currents in the face of low extracellular GABA concentrations.

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