Behavioral and Genetic Evidence for GIRK Channels in the CNS: Role in Physiology, Pathophysiology, and Drug Addiction
- PMID: 26422988
- PMCID: PMC4769645
- DOI: 10.1016/bs.irn.2015.05.016
Behavioral and Genetic Evidence for GIRK Channels in the CNS: Role in Physiology, Pathophysiology, and Drug Addiction
Abstract
G protein-coupled inwardly rectifying potassium (GIRK) channels are widely expressed throughout the brain and mediate the inhibitory effects of many neurotransmitters. As a result, these channels are important for normal CNS function and have also been implicated in Down syndrome, Parkinson's disease, psychiatric disorders, epilepsy, and drug addiction. Knockout mouse models have provided extensive insight into the significance of GIRK channels under these conditions. This review examines the behavioral and genetic evidence from animal models and genetic association studies in humans linking GIRK channels with CNS disorders. We further explore the possibility that subunit-selective modulators and other advanced research tools will be instrumental in establishing the role of individual GIRK subunits in drug addiction and other relevant CNS diseases and in potentially advancing treatment options for these disorders.
Keywords: Anxiety; Cocaine; Depression; Down syndrome; Epilepsy; Ethanol; Genetic association studies; Knockout mice; Opioids; Parkinson's disease; Schizophrenia; Sedative–hypnotics.
© 2015 Elsevier Inc. All rights reserved.
References
-
- Addolorato G, Leggio L, Ferrulli A, Cardone S, Bedogni G, Caputo F, et al. Dose–response effect of baclofen in reducing daily alcohol intake in alcohol dependence: Secondary analysis of a randomized, double-blind, placebo-controlled trial. Alcohol and Alcoholism. 2011;46(3):312–317. http://dx.doi.org/10.1093/alcalc/agr017. - DOI - PubMed
-
- Addolorato G, Leggio L, Hopf FW, Diana M, Bonci A. Novel therapeutic strategies for alcohol and drug addiction: Focus on GABA, ion channels and transcranial magnetic stimulation. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology. 2012;37(1):163–177. http://dx.doi.org/10.1038/npp.2011.216. - DOI - PMC - PubMed
-
- Anderson GR, Posokhova E, Martemyanov KA. The R7 RGS protein family: Multi-subunit regulators of neuronal G protein signaling. Cell Biochemistry and Biophysics. 2009;54(1–3):33–46. http://dx.doi.org/10.1007/s12013-009-9052-9. - DOI - PMC - PubMed
-
- Arora D, Haluk DM, Kourrich S, Pravetoni M, Fernandez-Alacid L, Nicolau JC, et al. Altered neurotransmission in the mesolimbic reward system of Girk mice. Journal of Neurochemistry. 2010;114(5):1487–1497. http://dx.doi.org/10.1111/j.1471-4159.2010.06864.x. - DOI - PMC - PubMed
-
- Aryal P, Dvir H, Choe S, Slesinger PA. A discrete alcohol pocket involved in GIRK channel activation. Nature Neuroscience. 2009;12(8):988–995. http://dx.doi.org/10.1038/nn.2358. - DOI - PMC - PubMed
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