Endogenous regulators of G protein signaling proteins regulate presynaptic inhibition at rat hippocampal synapses

Huanmian Chen, Nevin A. Lambert

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Presynaptic inhibition mediated by G protein-coupled receptors (GPCRs) can develop and decay in a few seconds. This time course is too rapid to be accounted for by the intrinsic GTPase activity of Gα subunits alone. Here, we test the hypothesis that endogenous regulators of G protein signaling (RGS proteins) are required for rapid, brief presynaptic inhibition. Endogenous G protein α subunits were uncoupled from GPCRs by treating cultures with pertussis toxin (PTX). Adenoviral expression of mutant PTX-insensitive (PTX-i) Gα(i1-3) or Gα(o) subunits rescued adenosine-induced presynaptic inhibition in cultured hippocampal neurons. Expression of double mutant Gα(i1) or Gα(o) subunits that were both PTX-insensitive and unable to bind RGS proteins (PTX/RGS-i) also rescued presynaptic inhibition. Presynaptic inhibition mediated by PTX/RGS-i subunits decayed much more slowly after agonist removal than that mediated by PTX-i subunits or native G proteins. The onset of presynaptic inhibition mediated by PTX/RGS-i Gα(o) was also slower than that mediated by PTX-i Gα(o). In contrast, the onset of presynaptic inhibition mediated by PTX/RGS-i Gα(i1) was similar to that mediated by PTX-i Gα(i1). These results suggest that endogenous RGS proteins regulate the time course of G protein signaling in mammalian central nervous system presynaptic terminals.

Original languageEnglish (US)
Pages (from-to)12810-12815
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number23
DOIs
StatePublished - Nov 7 2000

ASJC Scopus subject areas

  • General

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