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Rapid activation of inwardly rectifying potassium channels by immobile G-protein-coupled receptors.

Rapid activation of inwardly rectifying potassium channels by immobile G-protein-coupled receptors. Research Abstract Details 

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  • Rapid activation of inwardly rectifying potassium channels by immobile G-protein-coupled receptors. Abstract Text:

    robert m loberRobert M Lober,miguel a pereiraMiguel A Pereira,nevin a lambertNevin A Lambert,

    G-protein-coupled receptors (GPCRs) mediate slow synaptic transmission and many other effects of small molecule and peptide neurotransmitters. In the standard model of GPCR signaling, receptors and G-proteins diffuse laterally within the plane of the plasma membrane and encounter each other by random collision. This model predicts that signaling will be most efficient if both GPCRs and G-proteins are free to diffuse, thus maximizing collision frequency. However, neuronal GPCRs are often recruited to and enriched at specific synaptic locations, suggesting receptor mobility is restricted in these cells. Here, we test the hypothesis that restricting GPCR mobility impairs signaling in neurons by limiting the frequency of collisions between receptors and G-proteins. Mu-opioid receptors (MORs) were immobilized on the surface of cerebellar granule neurons by avidin-mediated cross-linking, and inwardly rectifying potassium (GIRK) channels were used as rapid indicators of G-protein activation. Mobile and immobile MORs activated GIRK channels with the same onset kinetics and agonist sensitivity in these neurons. In a heterologous expression system, GFP (green fluorescent protein)-tagged G alpha(oA) subunits remained mobile after cross-linking, but their mobility was reduced in the presence of immobile MORs, suggesting that these receptors and subunits were transiently precoupled. In addition, channel activation could be reconstituted with immobile GPCRs, G-protein heterotrimers, and GIRK channels. These results show that collision frequency is not rate-limiting for G-protein activation in CNS neurons, and are consistent with the idea that signaling components are compartmentalized or preassembled.

    Rapid activation of inwardly rectifying potassium channels by immobile G-protein-coupled receptors. Publishing Authors By Initials

    rm loberRM Lober,ma pereiraMA Pereira,na lambertNA Lambert,

    For similar synaptic transmission research abstracts see: synaptic transmission research

    PUBMED ID PMID:

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    Rapid activation of inwardly rectifying potassium channels by immobile G-protein-coupled receptors. Journal Published:

    PUBLICATION TYPE: Research Support, U.S. Gov't,

    Journal: The Journal of neuroscience : the official journal

    VOLUME: 26

    Page Numbers: 12602-8

    Journal Abbreviation: J. Neurosci.

    ISSN: 1529-2401

    DAY: 29

    MONTH: Nov

    YEAR: 2006

    Rapid activation of inwardly rectifying potassium channels by immobile G-protein-coupled receptors. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 8102140

    Rapid activation of inwardly rectifying potassium channels by immobile G-protein-coupled receptors. Keywords Mesh Terms:

    KEYWORDS: Synaptic Transmission

    MESH TERMS: physiology

    Chemical & Substance for Abstract: Rapid activation of inwardly rectifying potassium channels by immobile G-protein-coupled receptors. Information

    Substance Name: Receptors, G-Protein-Coupled

    Registry Number: 0

    Grant and Affiliation Information for Rapid activation of inwardly rectifying potassium channels by immobile G-protein-coupled receptors.

    AFFILIATION: Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, Georgia 30809, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NINDS

    GRANT: NS36455

    ACRONYM: NS

    MEDLINETA: J Neurosci

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    ACCESSION NUMBER:

    Number Hits: 0

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