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标题：RGS9-2 modulates D2 dopamine receptor-mediated Ca2+ channel inhibition in rat striatal cholinergic interneurons
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作者：Theresa M. Cabrera-Vera ; Salvador Hernandez ; Laurie R. Earls 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：46
页码：16339-16344
DOI：10.1073/pnas.0407416101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Regulator of G protein signaling (RGS) proteins negatively regulate receptor-mediated second messenger responses by enhancing the GTPase activity of G{alpha} subunits. We describe a receptor-specific role for an RGS protein at the level of an individual brain neuron. RGS9-2 and G{beta}5 mRNA and protein complexes were detected in striatal cholinergic and {gamma}-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.
关键词：calcium ; GTPase activating protein ; receptor-specific ; basal ganglia ; indirect pathway