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This Article Full Text Full Text (PDF) Supplemental data All Versions of this Article: 580/2/411    most recent jphysiol.2006.125914v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sohn, J.-W. Articles by Ho, W.-K. Search for Related Content PubMed PubMed Citation Articles by Sohn, J.-W. Articles by Ho, W.-K. Related Collections Neuroscience

¹ National Research Laboratory for Cell Physiology and Department of Physiology, Seoul National University College of Medicine, Jongno-gu, Seoul 110-799, Korea
² Department of Physiology, Sungtyunkwan University School of Medicine, Suwon 440-746, Korea
³ Department of Physiology, Gachon University of Medicine and Science School of Medicine, Incheon 406-799, Korea
⁴ Center for Neural Science, Korea Institute of Science and Technology, Seongbuk-gu, Seoul 136-791, Korea

It has been shown that the activation of G_q-coupled receptors (G_qPCRs) in cardiac myocytes inhibits the G protein-gated inwardly rectifying K⁺ current (I_GIRK) via receptor-specific depletion of phosphatidylinositol 4,5-bisphosphate (PIP₂). 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 PLC1 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 A₂ (PLA₂), 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 PLA₂-dependent production of arachidonic acid. These results present a novel receptor-specific mechanism for crosstalk between G_qPCRs and GABA_B receptors.

(Received 1 December 2006; accepted after revision 25 January 2007; first published online 25 January 2007)
Corresponding author W-K. Ho: Department of Physiology, Seoul National University College of Medicine, 28 Yonkeun-Dong, Jongno-gu, Seoul 110-799, Korea.  Email: wonkyung{at}snu.ac.kr

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