Gαi Controls the Gating of the G Protein-Activated K+ Channel, GIRK
Autor: | Dalia Varon, Tatiana Ivanina, Sagit Peleg, Carmen W. Dessauer, Nathan Dascal |
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Rok vydání: | 2002 |
Předmět: |
medicine.medical_specialty
Potassium Channels G protein GTP-Binding Protein alpha Subunits Neuroscience(all) Gi alpha subunit Alpha (ethology) Down-Regulation Gene Expression Gating GTP-Binding Protein alpha Subunits Gi-Go Synaptic Transmission Membrane Potentials Xenopus laevis Internal medicine Proto-Oncogene Proteins medicine Animals G protein-coupled inwardly-rectifying potassium channel RNA Messenger Potassium Channels Inwardly Rectifying Beta (finance) Neurotransmitter Agents Receptor Muscarinic M2 Binding Sites Chemistry urogenital system General Neuroscience Immunohistochemistry Receptors Muscarinic Cell biology Protein Structure Tertiary G beta-gamma complex Endocrinology G Protein-Coupled Inwardly-Rectifying Potassium Channels Guanosine 5'-O-(3-Thiotriphosphate) Oocytes Female GTP-Binding Protein alpha Subunit Gi2 Oligoribonucleotides Antisense |
Zdroj: | Neuron. 33(1):87-99 |
ISSN: | 0896-6273 |
DOI: | 10.1016/s0896-6273(01)00567-0 |
Popis: | GIRK (Kir3) channels are activated by neurotransmitters coupled to G proteins, via a direct binding of G(beta)(gamma). The role of G(alpha) subunits in GIRK gating is elusive. Here we demonstrate that G(alpha)(i) is not only a donor of G(beta)(gamma) but also regulates GIRK gating. When overexpressed in Xenopus oocytes, GIRK channels show excessive basal activity and poor activation by agonist or G(beta)(gamma). Coexpression of G(alpha)(i3) or G(alpha)(i1) restores the correct gating parameters. G(alpha)(i) acts neither as a pure G(beta)(gamma) scavenger nor as an allosteric cofactor for G(beta)(gamma). It inhibits only the basal activity without interfering with G(beta)(gamma)-induced response. Thus, GIRK is regulated, in distinct ways, by both arms of the G protein. G(alpha)(i) probably acts in its GDP bound form, alone or as a part of G(alpha)(beta)(gamma) heterotrimer. |
Databáze: | OpenAIRE |
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