Developmental regulation of G protein-gated inwardly-rectifying K+ (GIRK/Kir3) channel subunits in the brain.
Developmental regulation of G protein-gated inwardly-rectifying K+ (GIRK/Kir3) channel subunits in the brain.
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DOI：
10.1111/j.1460-9568.2011.07886.x
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Luján R
中科院分区：
文献类型：
--
作者：
Fernández-Alacid L;Watanabe M;Molnár E;Wickman K;Luján R
G蛋白门控内向整流K+通道（GIRK/family 3 of inwardly-rectified K+ channels）与神经递质作用偶联，在调节神经元兴奋性中发挥重要作用。我们研究了时间和空间的表达GIRK 1，GIRK 2和GIRK 3亚基在发育和成年啮齿类动物的大脑使用生化，免疫组织化学和免疫电镜技术。在分析的所有年龄组中，GIRK 1 -3的总体分布模式非常相似，在新皮质、小脑、海马和丘脑中表达水平较高。集中在海马，组织印迹和免疫组化显示，GIRK 1 -3蛋白水平随着年龄的增长而增加，这是伴随着亚基的亚细胞定位的转变。在发育早期（出生后第5天），GIRK亚基主要定位于锥体细胞的内质网，但出生后第60天，他们主要被发现沿着质膜。在发育过程中，GIRK 1和GIRK 2主要在突触后位点发现，而GIRK 3主要在突触前位点检测到。此外，GIRK 1和GIRK 2在脊柱质膜上的表达显示出与GIRK 3分布不同的相同的近端至远端梯度。此外，虽然GIRK 1从来没有发现在突触后密度（PSD），GIRK 2在PSD中的水平进行性增加，GIRK 3在PSD中没有变化。总之，这些发现揭示了神经元GIRK通道的发育调控和亚细胞多样性的新的光，并支持GIRK通道的不同亚群对神经元兴奋性产生可分离的影响的论点。选择性靶向GIRK通道的特定亚群的能力可能证明在治疗兴奋性障碍中是有效的。
G protein-gated inwardly-rectifying K+ (GIRK/family 3 of inwardly-rectifying K+) channels are coupled to neurotransmitter action and can play important roles in modulating neuronal excitability. We investigated the temporal and spatial expression of GIRK1, GIRK2 and GIRK3 subunits in the developing and adult rodent brain using biochemical, immunohistochemical and immunoelectron microscopic techniques. At all ages analysed, the overall distribution patterns of GIRK1-3 were very similar, with high expression levels in the neocortex, cerebellum, hippocampus and thalamus. Focusing on the hippocampus, histoblotting and immunohistochemistry showed that GIRK1-3 protein levels increased with age, and this was accompanied by a shift in the subcellular localization of the subunits. Early in development (postnatal day 5), GIRK subunits were predominantly localized to the endoplasmic reticulum in the pyramidal cells, but by postnatal day 60 they were mostly found along the plasma membrane. During development, GIRK1 and GIRK2 were found primarily at postsynaptic sites, whereas GIRK3 was predominantly detected at presynaptic sites. In addition, GIRK1 and GIRK2 expression on the spine plasma membrane showed identical proximal-to-distal gradients that differed from GIRK3 distribution. Furthermore, although GIRK1 was never found within the postsynaptic density (PSD), the level of GIRK2 in the PSD progressively increased and GIRK3 did not change in the PSD during development. Together, these findings shed new light on the developmental regulation and subcellular diversity of neuronal GIRK channels, and support the contention that distinct subpopulations of GIRK channels exert separable influences on neuronal excitability. The ability to selectively target specific subpopulations of GIRK channels may prove effective in the treatment of disorders of excitability.
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影响因子：
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作者：
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通讯作者：
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