TY - JOUR
T1 - GABA-Independent GABAA Receptor Openings Maintain Tonic Currents
AU - Wlodarczyk, Agnieszka I.
AU - Sylantyev, Sergiy
AU - Herd, Murray B.
AU - Kersanté, Flavie
AU - Lambert, Jeremy J.
AU - Rusakov, Dmitri A.
AU - Linthorst, Astrid C.E.
AU - Semyanov, Alexey
AU - Belelli, Delia
AU - Pavlov, Ivan
AU - Walker, Matthew C.
PY - 2013/2/27
Y1 - 2013/2/27
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84874596634&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.4193-12.2013
DO - 10.1523/JNEUROSCI.4193-12.2013
M3 - Article
C2 - 23447601
AN - SCOPUS:84874596634
SN - 0270-6474
VL - 33
SP - 3905
EP - 3914
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 9
ER -