PubMed 15534226

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Cav2.2

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

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

Journal, date & volume: Proc. Natl. Acad. Sci. U.S.A., 2004 Nov 16 , 101, 16339-44

PubMed link:

Regulator of G protein signaling (RGS) proteins negatively regulate receptor-mediated second messenger responses by enhancing the GTPase activity of Galpha subunits. We describe a receptor-specific role for an RGS protein at the level of an individual brain neuron. RGS9-2 and Gbeta(5) mRNA and protein complexes were detected in striatal cholinergic and gamma-aminobutyric acidergic neurons. Dialysis of cholinergic neurons with RGS9 constructs enhanced basal Ca(2+) channel currents and reduced D(2) dopamine receptor modulation of Cav2.2 channels. These constructs did not alter M(2) muscarinic receptor modulation of Cav2.2 currents in the same neuron. The noncatalytic DEP-GGL domain of RGS9 antagonized endogenous RGS9-2 activity, enhancing D(2) receptor modulation of Ca(2+) 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.