GABA-Independent GABAA Receptor Openings Maintain Tonic Currents

Agnieszka I. Wlodarczyk*, Sergiy Sylantyev, Murray B. Herd, Flavie Kersanté, Jeremy J. Lambert, Dmitri A. Rusakov, Astrid C. E. Linthorst, Alexey Semyanov, Delia Belelli, Ivan Pavlov, Matthew C. Walker

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

81 Citations (Scopus)


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 perisynaptic 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 (gabazine), 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 CSF 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
Number of pages11
JournalJournal of Neuroscience
Issue number9
Publication statusPublished - 27 Feb 2013

Bibliographical note

This work was supported by Wellcome Trust Grants WT083163 (A.I.W., A.S., F.K., A.C.E.L., and M.C.W.) and WT084311 (D.A.R.); Medical Research Council Grants G10000008 (D.B. and J.J.L.), and G0900613 and G0802216 (D.A.R.); Tenovus Scotland (J.J.L. and D.B.); Anonymous Trust (J.J.L. and D.B.); Epilepsy Research UK Grants F1001 (M.B.H.) and A0832 (I.P.); and Worshipful Company of Pewterers (I.P.).


Dive into the research topics of 'GABA-Independent GABAA Receptor Openings Maintain Tonic Currents'. Together they form a unique fingerprint.

Cite this