中枢神经系统中GIRK通道的行为学和遗传学证据：在生理学、病理生理学及药物成瘾中的作用
Behavioral and Genetic Evidence for GIRK Channels in the CNS: Role in Physiology, Pathophysiology, and Drug Addiction.
作者信息
Mayfield Jody, Blednov Yuri A, Harris R Adron
机构信息
Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas, USA.
Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas, USA.
出版信息
Int Rev Neurobiol. 2015;123:279-313. doi: 10.1016/bs.irn.2015.05.016. Epub 2015 Jun 22.
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.
摘要
G蛋白偶联内向整流钾通道（GIRK通道）在全脑广泛表达，并介导多种神经递质的抑制作用。因此，这些通道对中枢神经系统的正常功能很重要，并且与唐氏综合征、帕金森病、精神疾病、癫痫和药物成瘾也有关联。基因敲除小鼠模型为深入了解这些情况下GIRK通道的重要性提供了广泛的见解。这篇综述考察了来自动物模型的行为和遗传学证据以及人类遗传学关联研究，这些研究将GIRK通道与中枢神经系统疾病联系起来。我们进一步探讨了亚基选择性调节剂和其他先进研究工具在确定单个GIRK亚基在药物成瘾和其他相关中枢神经系统疾病中的作用以及在潜在推进这些疾病的治疗选择方面发挥作用的可能性。
相似文献
1
Behavioral and Genetic Evidence for GIRK Channels in the CNS: Role in Physiology, Pathophysiology, and Drug Addiction.中枢神经系统中GIRK通道的行为学和遗传学证据：在生理学、病理生理学及药物成瘾中的作用
Int Rev Neurobiol. 2015;123:279-313. doi: 10.1016/bs.irn.2015.05.016. Epub 2015 Jun 22.
2
Emerging roles for G protein-gated inwardly rectifying potassium (GIRK) channels in health and disease.G 蛋白门控内向整流钾 (GIRK) 通道在健康和疾病中的新兴作用。
Nat Rev Neurosci. 2010 May;11(5):301-15. doi: 10.1038/nrn2834. Epub 2010 Apr 14.
3
Modulators of G protein-activated inwardly rectifying K+ channels: potentially therapeutic agents for addictive drug users.G蛋白激活的内向整流钾通道调节剂：成瘾药物使用者的潜在治疗药物。
Ann N Y Acad Sci. 2004 Oct;1025:590-4. doi: 10.1196/annals.1316.073.
4
Identification of a G-Protein-Independent Activator of GIRK Channels.GIRK通道的一种不依赖G蛋白的激活剂的鉴定。
Cell Rep. 2020 Jun 16;31(11):107770. doi: 10.1016/j.celrep.2020.107770.
5
GIRK Channel Plasticity and Implications for Drug Addiction.GIRK通道可塑性及其对药物成瘾的影响。
Int Rev Neurobiol. 2015;123:201-38. doi: 10.1016/bs.irn.2015.05.011. Epub 2015 Jun 22.
6
G protein-activated inwardly rectifying potassium channels as potential therapeutic targets.G蛋白激活的内向整流钾通道作为潜在的治疗靶点。
Curr Pharm Des. 2006;12(34):4513-23. doi: 10.2174/138161206779010468.
7
Deletion of GIRK2 Subunit of GIRK Channels Alters the 5-HT1A Receptor-Mediated Signaling and Results in a Depression-Resistant Behavior.GIRK通道GIRK2亚基的缺失改变5-HT1A受体介导的信号传导并导致抗抑郁行为。
Int J Neuropsychopharmacol. 2015 May 8;18(11):pyv051. doi: 10.1093/ijnp/pyv051.
8
New insights into the therapeutic potential of Girk channels.Girk 通道治疗潜力的新见解。
Trends Neurosci. 2014 Jan;37(1):20-9. doi: 10.1016/j.tins.2013.10.006. Epub 2013 Nov 21.
9
G Protein-Gated Potassium Channels: A Link to Drug Addiction.G蛋白门控钾通道：与药物成瘾的联系。
Trends Pharmacol Sci. 2017 Apr;38(4):378-392. doi: 10.1016/j.tips.2017.01.007. Epub 2017 Feb 7.
10
Behavioral characterization of mice lacking GIRK/Kir3 channel subunits.缺乏GIRK/Kir3通道亚基的小鼠的行为特征
Genes Brain Behav. 2008 Jul;7(5):523-31. doi: 10.1111/j.1601-183X.2008.00388.x.
引用本文的文献
1
Common Genomic and Proteomic Alterations Related to Disturbed Neural Oscillatory Activity in Schizophrenia.与精神分裂症中神经振荡活动紊乱相关的常见基因组和蛋白质组改变
Int J Mol Sci. 2025 Aug 4;26(15):7514. doi: 10.3390/ijms26157514.
2
Potassium channels in depression: emerging roles and potential targets.抑郁症中的钾通道：新出现的作用和潜在靶点。
Cell Biosci. 2024 Nov 11;14(1):136. doi: 10.1186/s13578-024-01319-0.
3
Comparing CB1 receptor GIRK channel responses to receptor internalization using a kinetic imaging assay.使用动力学成像测定法比较 CB1 受体 GIRK 通道反应与受体内化。
Sci Rep. 2024 Aug 7;14(1):18314. doi: 10.1038/s41598-024-68451-2.
4
Integrated bioinformatics analysis for exploring potential biomarkers related to Parkinson's disease progression.整合生物信息学分析以探索与帕金森病进展相关的潜在生物标志物。
BMC Med Genomics. 2024 May 17;17(1):133. doi: 10.1186/s12920-024-01885-9.
5
Upregulated GIRK2 Counteracts Ethanol-Induced Changes in Excitability and Respiration in Human Neurons.GIRK2 的上调可拮抗乙醇诱导的人神经元兴奋性和呼吸变化。
J Neurosci. 2024 Apr 17;44(16):e0918232024. doi: 10.1523/JNEUROSCI.0918-23.2024.
6
Identification of Hub Genes and Potential Molecular Pathogenesis in Substantia Nigra in Parkinson's Disease via Bioinformatics Analysis.通过生物信息学分析鉴定帕金森病黑质中的枢纽基因及潜在分子发病机制
Parkinsons Dis. 2023 Apr 14;2023:6755569. doi: 10.1155/2023/6755569. eCollection 2023.
7
Chronic Intermittent Ethanol Exposure Alters Behavioral Flexibility in Aged Rats Compared to Adult Rats and Modifies Protein and Protein Pathways Related to Alzheimer's Disease.与成年大鼠相比，慢性间歇性乙醇暴露会改变老年大鼠的行为灵活性，并改变与阿尔茨海默病相关的蛋白质和蛋白质通路。
ACS Omega. 2022 Dec 7;7(50):46260-46276. doi: 10.1021/acsomega.2c04528. eCollection 2022 Dec 20.
8
Atypical hypnotic compound ML297 restores sleep architecture immediately following emotionally valenced learning, to promote memory consolidation and hippocampal network activation during recall.非典型催眠化合物 ML297 在情绪相关学习后立即恢复睡眠结构，以促进记忆巩固和海马体网络在回忆时的激活。
Sleep. 2023 Mar 9;46(3). doi: 10.1093/sleep/zsac301.
9
Chronic Cerebral Hypoperfusion-induced Dysregulations of Hyperpolarization- activated Cyclic Nucleotide-gated, KCNQ and G Protein-coupled Inwardly Rectifying Potassium Channels Correlated with Susceptibility and Unsusceptibility to Anxiety Behaviors.慢性脑灌注不足诱导的超极化激活环核苷酸门控通道、KCNQ通道和G蛋白偶联内向整流钾通道的失调与焦虑行为易感性和不易感性相关。
Curr Neurovasc Res. 2022;19(4):398-405. doi: 10.2174/1567202620666221025152325.
10
Enhanced GIRK2 channel signaling in Down syndrome: A feasible role in the development of abnormal nascent neural circuits.唐氏综合征中增强的GIRK2通道信号传导：在新生神经回路异常发育中的可能作用。
Front Genet. 2022 Sep 12;13:1006068. doi: 10.3389/fgene.2022.1006068. eCollection 2022.
本文引用的文献
1
GIRK3 gates activation of the mesolimbic dopaminergic pathway by ethanol.GIRK3通过乙醇控制中脑边缘多巴胺能通路的激活。
Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):7091-6. doi: 10.1073/pnas.1416146112. Epub 2015 May 11.
2
Deletion of GIRK2 Subunit of GIRK Channels Alters the 5-HT1A Receptor-Mediated Signaling and Results in a Depression-Resistant Behavior.GIRK通道GIRK2亚基的缺失改变5-HT1A受体介导的信号传导并导致抗抑郁行为。
Int J Neuropsychopharmacol. 2015 May 8;18(11):pyv051. doi: 10.1093/ijnp/pyv051.
3
GIRK Channels Modulate Opioid-Induced Motor Activity in a Cell Type- and Subunit-Dependent Manner.GIRK通道以细胞类型和亚基依赖的方式调节阿片类药物诱导的运动活动。
J Neurosci. 2015 May 6;35(18):7131-42. doi: 10.1523/JNEUROSCI.5051-14.2015.
4
Major depressive disorder: mechanism-based prescribing for personalized medicine.重度抑郁症：基于机制的个性化药物处方
Neuropsychiatr Dis Treat. 2015 Mar 31;11:875-88. doi: 10.2147/NDT.S73261. eCollection 2015.
5
Glutamatergic synaptic plasticity in the mesocorticolimbic system in addiction.中脑边缘多巴胺系统中的谷氨酸突触可塑性与成瘾。
Front Cell Neurosci. 2015 Jan 20;8:466. doi: 10.3389/fncel.2014.00466. eCollection 2014.
6
Regulator of G protein signaling 6 is a critical mediator of both reward-related behavioral and pathological responses to alcohol.G蛋白信号调节因子6是酒精奖励相关行为和病理反应的关键介质。
Proc Natl Acad Sci U S A. 2015 Feb 17;112(7):E786-95. doi: 10.1073/pnas.1418795112. Epub 2015 Feb 2.
7
Keppen-Lubinsky syndrome is caused by mutations in the inwardly rectifying K+ channel encoded by KCNJ6.凯彭-卢宾斯基综合征由KCNJ6编码的内向整流钾通道突变引起。
Am J Hum Genet. 2015 Feb 5;96(2):295-300. doi: 10.1016/j.ajhg.2014.12.011. Epub 2015 Jan 22.
8
Rapid antidepressants stimulate the decoupling of GABA(B) receptors from GIRK/Kir3 channels through increased protein stability of 14-3-3η.快速起效的抗抑郁药通过提高14-3-3η的蛋白质稳定性，刺激GABA(B)受体与GIRK/Kir3通道解偶联。
Mol Psychiatry. 2015 Mar;20(3):298-310. doi: 10.1038/mp.2014.165. Epub 2015 Jan 6.
9
Peroxisome proliferator-activated receptors α and γ are linked with alcohol consumption in mice and withdrawal and dependence in humans.过氧化物酶体增殖物激活受体α和γ与小鼠的酒精摄入以及人类的戒酒和成瘾有关。
Alcohol Clin Exp Res. 2015 Jan;39(1):136-45. doi: 10.1111/acer.12610. Epub 2014 Dec 16.
10
Association between KCNJ6 (GIRK2) gene polymorphism rs2835859 and post-operative analgesia, pain sensitivity, and nicotine dependence.KCNJ6（GIRK2）基因多态性rs2835859与术后镇痛、疼痛敏感性及尼古丁依赖之间的关联
J Pharmacol Sci. 2014;126(3):253-63. doi: 10.1254/jphs.14189fp. Epub 2014 Oct 25.
Zotero 插件