Inhibition of a Gi-activated Potassium Channel (GIRK1/4) by the Gq-coupled m1 Muscarinic Acetylcholine Receptor
| Autor: | Ernest G. Peralta, Jennifer J. Hill |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Potassium Channels
Pharmacology Second Messenger Systems Biochemistry GTP-Binding Protein gamma Subunits Muscarinic acetylcholine receptor M5 Muscarinic acetylcholine receptor Potassium Channel Blockers Muscarinic acetylcholine receptor M4 Calcium Signaling G protein-coupled inwardly-rectifying potassium channel Cloning Molecular Phosphorylation Potassium Channels Inwardly Rectifying Molecular Biology Protein Kinase C biology Chemistry GTP-Binding Protein beta Subunits Receptor Muscarinic M1 Electric Conductivity Muscarinic acetylcholine receptor M3 Muscarinic acetylcholine receptor M2 Cell Biology Muscarinic acetylcholine receptor M1 Heterotrimeric GTP-Binding Proteins Receptors Muscarinic Recombinant Proteins Protein Structure Tertiary Cell biology Electrophysiology G Protein-Coupled Inwardly-Rectifying Potassium Channels Gq alpha subunit biology.protein GTP-Binding Protein alpha Subunits Gq-G11 |
| Zdroj: | Journal of Biological Chemistry. 276:5505-5510 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m008213200 |
| Popis: | The G protein-coupled inwardly rectifying K+ channel, GIRK1/GIRK4, can be activated by receptors coupled to the Galpha(i) subunit. An opposing role for Galpha(q) receptor signaling in GIRK regulation has only recently begun to be established. We have studied the effects of m1 muscarinic acetylcholine receptor (mAChR) stimulation, which is known to mobilize calcium and activate protein kinase C (PKC) by a Galpha(q)-dependent mechanism, on whole cell GIRK1/4 currents in Xenopus oocytes. We found that stimulation of the m1 mAChR suppresses both basal and dopamine 2 receptor-activated GIRK 1/4 currents. Overexpression of Gbetagamma subunits attenuates this effect, suggesting that increased binding of Gbetagamma to the GIRK channel can effectively compete with the G(q)-mediated inhibitory signal. This G(q) signal requires the use of second messenger molecules; pharmacology implicates a role for PKC and Ca2+ responses as m1 mAChR-mediated inhibition of GIRK channels is mimicked by PMA and Ca2+ ionophore. We have analyzed a series of mutant and chimeric channels suggesting that the GIRK4 subunit is capable of responding to G(q) signals and that the resulting current inhibition does not occur via phosphorylation of a canonical PKC site on the channel itself. |
| Databáze: | OpenAIRE |
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