title: Receptor-specific inhibition of GABAB-activated K+ currents by muscarinic and metabotropic glutamate receptors in immature rat hippocampus.
abstract: It has been shown that the activation of G(q)-coupled receptors (G(q)PCRs) in cardiac myocytes inhibits the G protein-gated inwardly rectifying K(+) current (I(GIRK)) via receptor-specific depletion of phosphatidylinositol 4,5-bisphosphate (PIP(2)). In this study, we investigated the mechanism of the receptor-mediated regulation of I(GIRK) in acutely isolated hippocampal CA1 neurons by the muscarinic receptor agonist, carbachol (CCh), and the group I metabotropic glutamate receptor (mGluR) agonist, 3,5-dihydroxyphenylglycine (DHPG). I(GIRK) was activated by the GABA(B) receptor agonist, baclofen. When baclofen was repetitively applied at intervals of 2-3 min, the amplitude of the second I(GIRK) was 92.3 +/- 1.7% of the first I(GIRK) in control. Pretreatment of neurons with CCh or DHPG prior to the second application of baclofen caused a reduction in the amplitude of the second I(GIRK) to 54.8 +/- 1.3% and 51.4 +/- 0.6%, respectively. In PLCbeta1 knockout mice, the effect of CCh on I(GIRK) was significantly reduced, whereas the effect of DHPG remained unchanged. The CCh-mediated inhibition of I(GIRK) was almost completely abolished by PKC inhibitors and pipette solutions containing BAPTA. The DHPG-mediated inhibition of I(GIRK) was attenuated by the inhibition of phospholipase A(2) (PLA(2)), or the sequestration of arachidonic acid. We confirmed that DHPG eliminated the inhibition of I(GIRK) by arachidonic acid. These results indicate that muscarinic inhibition of I(GIRK) is mediated by the PLC/PKC signalling pathway, while group I mGluR inhibition of I(GIRK) occurs via the PLA(2)-dependent production of arachidonic acid. These results present a novel receptor-specific mechanism for crosstalk between G(q)PCRs and GABA(B) receptors.
authors.affiliation: Department of Physiology, Seoul National University College of Medicine, 28 Yonkeun-Dong, Jongno-gu, Seoul 110-799, Korea.
authors.forename: Jong-Woo
authors.initials: JW
authors.lastname: Sohn
authors.forename: Doyun
authors.initials: D
authors.lastname: Lee
authors.forename: Hana
authors.initials: H
authors.lastname: Cho
authors.forename: Wonil
authors.initials: W
authors.lastname: Lim
authors.forename: Hee-Sup
authors.initials: HS
authors.lastname: Shin
authors.forename: Suk-Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Won-Kyung
authors.initials: WK
authors.lastname: Ho
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001418:Baclofen / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000378:metabolism*; D058788:GABA-B Receptor Antagonists; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D018721:Muscarinic Agonists / Q000494:pharmacology; D054799:Phospholipase C beta; D010741:Phospholipases A / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D058788:GABA-B Receptor Antagonists; D007527:Isoenzymes; D018721:Muscarinic Agonists; D018094:Receptors, Metabotropic Glutamate; D011976:Receptors, Muscarinic; D016718:Arachidonic Acid; D008734:Methoxyhydroxyphenylglycol; D002217:Carbachol; D011493:Protein Kinase C; D010741:Phospholipases A; D010738:Type C Phospholipases; D054799:Phospholipase C beta; D001418:Baclofen; D011188:Potassium; D002118:Calcium; C010117:3,4-dihydroxyphenylglycol; D000077191:Wortmannin