Receptors with different affinities mediate phasic and tonic GABA(A) conductances in hippocampal neurons.
A tonic inhibitory conductance mediated by GABA(A) receptors that supplements the phasic inhibition produced by IPSCs has been identified in the hippocampus and cerebellum. It is presently unknown whether tonic and phasic inhibitions are mediated by GABA(A) receptors with different subunit assemblies. Here we demonstrate that a low concentration (200 nm) of the highly specific competitive GABA(A) antagonist SR95531 (gabazine) reduces phasic inhibition in hippocampal granule cells by 71% but has no effect on tonic inhibition, whereas a high concentration (10 microm) of the antagonist blocked both conductances. These findings are consistent with tonic and phasic conductances being mediated by different GABA(A) receptor subtypes with different affinities for GABA.
Stell
Brandon M
BM
Department of Neurology, University of California Los Angeles School of Medicine, Los Angeles, California 90095, USA.
Mody
Istvan
I
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D011724:Pyridazines / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000145:classification / Q000378:metabolism*; D013379:Substrate Specificity / Q000502:physiology
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D011724:Pyridazines; D011963:Receptors, GABA-A; C049853:gabazine