Brain Localization and Behavioral Impact of the G-Protein-Gated K+ Channel Subunit GIRK4
Brain Localization and Behavioral Impact of the G-Protein-Gated K+ Channel Subunit GIRK4
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DOI：
10.1523/jneurosci.20-15-05608.2000
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发表时间：
2000-08
期刊：
影响因子：
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通讯作者：
K. Wickman;C. Karschin;A. Karschin;M. Picciotto;D. Clapham
中科院分区：
文献类型：
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作者：
K. Wickman;C. Karschin;A. Karschin;M. Picciotto;D. Clapham
神经元g蛋白门控钾（KG）通道被多种神经递质激活，是哺乳动物神经系统突触抑制的重要模式。KG通道由四个亚基组合而成，称为G蛋白门控内向纠偏K+通道（GIRK）。所有四个GIRK亚基都在大脑中表达，关于GIRK1、GIRK2和GIRK3的表达模式已经有了普遍的共识。然而，GIRK4的定位模式仍然存在争议。在这项研究中，我们利用缺乏功能性GIRK4基因的小鼠的阴性背景来鉴定含有GIRK4 mRNA的神经元群体。GIRK4 mRNA仅在小鼠大脑的少数区域检测到，包括皮质深部锥体神经元、岛叶皮质的梨状内核和屏状核、白球、下丘脑腹内侧核、束旁核和室旁核以及少数脑干核（如下橄榄核和前庭核）。缺乏GIRK4的小鼠存活，表现正常，在运动活动、视觉任务和疼痛感知方面没有明显缺陷。此外，girk4缺陷小鼠在被动回避范式（一项厌恶学习测试）中的表现与野生型对照组相似。然而，GIRK4基因敲除的小鼠在莫里斯水迷宫（Morris water maze，一项空间学习和记忆测试）中确实表现出受损的表现。
Neuronal G-protein-gated potassium (KG) channels are activated by several neurotransmitters and constitute an important mode of synaptic inhibition in the mammalian nervous system. KG channels are composed of combinations of four subunits termed G protein-gated inwardly rectifying K+channels (GIRK). All four GIRK subunits are expressed in the brain, and there is a general consensus concerning the expression patterns of GIRK1, GIRK2, and GIRK3. The localization pattern of GIRK4, however, remains controversial. In this study, we exploit the negative background of mice lacking a functional GIRK4 gene to identify neuronal populations that contain GIRK4 mRNA. GIRK4 mRNA was detected in only a few regions of the mouse brain, including the deep cortical pyramidal neurons, the endopiriform nucleus and claustrum of the insular cortex, the globus pallidus, the ventromedial hypothalamic nucleus, parafascicular and paraventricular thalamic nuclei, and a few brainstem nuclei (e.g., the inferior olive and vestibular nuclei). Mice lacking GIRK4 were viable and appeared normal and did not display gross deficiencies in locomotor activity, visual tasks, and pain perception. Furthermore, GIRK4-deficient mice performed similarly to wild-type controls in the passive avoidance paradigm, a test of aversive learning. GIRK4 knock-out mice did, however, exhibit impaired performance in the Morris water maze, a test of spatial learning and memory.