title: GABAB Receptors Regulate Extrasynaptic GABAA Receptors.
abstract: Tonic inhibitory GABA(A) receptor-mediated currents are observed in numerous cell types in the CNS, including thalamocortical neurons of the ventrobasal thalamus, dentate gyrus granule cells, and cerebellar granule cells. Here we show that in rat brain slices, activation of postsynaptic GABA(B) receptors enhances the magnitude of the tonic GABA(A) current recorded in these cell types via a pathway involving G G proteins, adenylate cyclase, and cAMP-dependent protein kinase. Using a combination of pharmacology and knockout mice, we show that this pathway is independent of potassium channels or GABA transporters. Furthermore, the enhancement in tonic current is sufficient to significantly alter the excitability of thalamocortical neurons. These results demonstrate for the first time a postsynaptic crosstalk between GABA(B) and GABA(A) receptors.
authors: Cardiff School of Biosciences, Cardiff University, Cardiff CF10 AX, United Kingdom. connellywm@cardiff.ac.uk
authors: William M
authors: WM
authors: Connelly
authors: Sarah J
authors: SJ
authors: Fyson
authors: Adam C
authors: AC
authors: Errington
authors: Cian P
authors: CP
authors: McCafferty
authors: David W
authors: DW
authors: Cope
authors: Giuseppe
authors: G
authors: Di Giovanni
authors: Vincenzo
authors: V
authors: Crunelli
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001703:Biophysics; D001921:Brain / Q000166:cytology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism / Q000494:pharmacology; 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; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000172:deficiency / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000172:deficiency / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D018682:GABA Agents; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D026941:Sodium Channel Blockers; D013873:Thionucleotides; D006153:Guanosine Diphosphate; C017759:9-(tetrahydro-2-furyl)-adenine; D013779:Tetrodotoxin; C023427:guanosine 5'-O-(2-thiodiphosphate); D017868:Cyclic AMP-Dependent Protein Kinases; D000225:Adenine