Differential subcellular localization of SK3-containing channels in the hippocampus
Differential subcellular localization of SK3-containing channels in the hippocampus
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DOI：
10.1111/ejn.12474
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发表时间：
2014-03-01
影响因子：
3.4
通讯作者：
Lujan, Rafael
中科院分区：
文献类型：
--
作者：
Ballesteros-Merino, Carmen;Watanabe, Masahiko;Lujan, Rafael
小电导、Ca 2+激活的K+（SK）通道在海马中表达，在海马中它们调节突触反应、可塑性以及学习和记忆。为了研究SK 3（KCNN 3）亚基的表达，我们使用Western印迹、免疫组织化学和高分辨率免疫电镜技术测定了发育中小鼠海马中SK 3的发育概况和亚细胞分布。结果表明，SK 3的表达在出生后的发展过程中增加，和SK 3的本地化从主要与内质网和细胞内的网站在出生后的第一周逐渐集中在树突棘在以后的阶段。在成人，SK 3主要定位于突触后室，无论是在突触外的网站和沿着突触后密度的兴奋性突触。双标记显示SK 3与SK2（KCNN 2）和N-甲基-D-天冬氨酸受体共定位。最后，SK 3密度的定量分析揭示了海马不同层中的两种亚细胞分布模式，SK 3在海马锥体细胞CA 1区分布不均匀，在齿状回颗粒细胞中分布均匀。我们的研究结果揭示了一个复杂的细胞表面分布SK 3含通道和一个独特的发展计划，可能会影响不同的海马功能。
Small-conductance, Ca2+-activated K+ (SK) channels are expressed in the hippocampus where they regulate synaptic responses, plasticity, and learning and memory. To investigate the expression of SK3 (KCNN3) subunits, we determined the developmental profile and subcellular distribution of SK3 in the developing mouse hippocampus using western blots, immunohistochemistry and high-resolution immunoelectron microscopy. The results showed that SK3 expression increased during postnatal development, and that the localization of SK3 changed from being mainly associated with the endoplasmic reticulum and intracellular sites during the first postnatal week to being progressively concentrated in dendritic spines during later stages. In the adult, SK3 was localized mainly in postsynaptic compartments, both at extrasynaptic sites and along the postsynaptic density of excitatory synapses. Double labelling showed that SK3 co-localized with SK2 (KCNN2) and with N-methyl-D-aspartate receptors. Finally, quantitative analysis of SK3 density revealed two subcellular distribution patterns in different hippocampal layers, with SK3 being unevenly distributed in CA1 region of the hippocampus pyramidal cells and homogeneously distributed in dentate gyrus granule cells. Our results revealed a complex cell surface distribution of SK3-containing channels and a distinct developmental program that may influence different hippocampal functions.