title: Postsynaptic GABAB receptors enhance extrasynaptic GABAA receptor function in dentate gyrus granule cells.
abstract: Ambient GABA in the brain tonically activates extrasynaptic GABA(A) receptors, and activity-dependent changes in ambient GABA concentration can also activate GABA(B) receptors. To investigate an interaction between postsynaptic GABA(B) and GABA(A) receptors, we recorded GABA(A) currents elicited by exogenous GABA (10 μm) from dentate gyrus granule cells (DGGCs) in adult rat hippocampal slices. The GABA(B) receptor agonist baclofen (20 μm) enhanced GABA(A) currents. This enhancement was blocked by the GABA(B) receptor antagonist CGP 55845 and intracellular solutions containing the GTP analog GDP-β-s, indicating that baclofen was acting on postsynaptic GABA(B) receptors. Modulation of GABA(A) currents by postsynaptic GABA(B) receptors was not observed in CA1 pyramidal cells or layer 2/3 cortical pyramidal neurons. Baclofen reduced the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) but did not alter sIPSC amplitude or kinetics. Thus, GABA(A) receptors activated at synapses were not modulated by postsynaptic GABA(B) receptors. In contrast, tonic GABA currents and currents activated by the GABA(A) receptor δ subunit-selective agonist THIP (10 μm) were potentiated by baclofen. Our data indicate that postsynaptic GABA(B) receptors enhance the function of extrasynaptic GABA(A) receptors, including δ subunit-containing receptors that mediate tonic inhibition in DGGCs. The modulation of GABA(A) receptor function by postsynaptic GABA(B) receptors is a newly identified mechanism that will influence the inhibitory tone of DGGCs when GABA(B) and GABA(A) receptors are both activated.
authors: Epilepsy Center of Excellence, Veterans Affairs Puget Sound Health Care System, Seattle, Washington 98108, USA.
authors: Wucheng
authors: W
authors: Tao
authors: Matthew H
authors: MH
authors: Higgs
authors: William J
authors: WJ
authors: Spain
authors: Christopher B
authors: CB
authors: Ransom
mesh_terms: D000818:Animals; D001703:Biophysics; D018891:Dentate Gyrus / Q000166:cytology*; D004347:Drug Interactions; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D018682:GABA Agents / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D018942:Macrolides / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D018682:GABA Agents; D018942:Macrolides; D013873:Thionucleotides; D006153:Guanosine Diphosphate; D005680:gamma-Aminobutyric Acid; C023427:guanosine 5'-O-(2-thiodiphosphate); C036978:concanamycin A; D006160:Guanosine Triphosphate