RGS9-2 modulates D2 dopamine receptor-mediated Ca2+ channel inhibition in rat striatal cholinergic interneurons

Theresa M. Cabrera-Vera, Salvador Hernandez, Laurie R. Earls, Martina Medkova, Anna K. Sundgren-Andersson, D. James Surmeier, Heidi E. Hamm*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

86 Scopus citations


Regulator of G protein signaling (RGS) proteins negatively regulate receptor-mediated second messenger responses by enhancing the GTPase activity of Gα subunits. We describe a receptor-specific role for an RGS protein at the level of an individual brain neuron. RGS9-2 and Gβ5 mRNA and protein complexes were detected in striatal cholinergic and γ-aminobutyric acidergic neurons. Dialysis of cholinergic neurons with RGS9 constructs enhanced basal Ca2+ channel currents and reduced D2 dopamine receptor modulation of Cav2.2 channels. These constructs did not alter M2 muscarinic receptor modulation of Cav2.2 currents in the same neuron. The noncatalytic DEP-GGL domain of RGS9 antagonized endogenous RGS9-2 activity, enhancing D2 receptor modulation of Ca2+ currents. In vitro, RGS9 constructs accelerated GTPase activity, in agreement with electrophysiological measurements, and did so more effectively at Go than Gi. These results implicate RGS9-2 as a specific regulator of dopamine receptor-mediated signaling in the striatum and identify a role for GAP activity modulation by the DEP-GGL domain.

Original languageEnglish (US)
Pages (from-to)16339-16344
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number46
StatePublished - Nov 16 2004


  • Basal ganglia
  • Calcium
  • GTPase activating protein
  • Indirect pathway
  • Receptor-specific

ASJC Scopus subject areas

  • General


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