GABA-Independent GABAA Receptor Openings Maintain Tonic Currents

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

Research output: Contribution to journalArticlepeer-review


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

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