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RGS9-2 modulates D 2 dopamine receptor-mediated Ca 2+ channel inhibition in rat striatal cholinergic interneurons

2004; National Academy of Sciences; Volume: 101; Issue: 46 Linguagem: Inglês

10.1073/pnas.0407416101

1091-6490

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

Ion channel regulation and function

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 Gβ 5 mRNA and protein complexes were detected in striatal cholinergic and γ-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.