Developmental profile of SK2 channel expression and function in CA1 neurons.
Developmental profile of SK2 channel expression and function in CA1 neurons.
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DOI：
10.1002/hipo.20986
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发表时间：
2012-06
期刊：
影响因子：
3.5
通讯作者：
Lujan, Rafael
中科院分区：
文献类型：
--
作者：
Ballesteros-Merino, Carmen;Lin, Mike;Wu, Wendy W.;Ferrandiz-Huertas, Clotilde;Cabanero, Maria J.;Watanabe, Masahiko;Fukazawa, Yugo;Shigemoto, Ryuichi;Maylie, James;Adelman, John P.;Lujan, Rafael
我们利用分子和生化技术、免疫金定量电子显微镜和电生理学技术研究了SK2在发育中的小鼠海马区的时空表达。编码SK2的基因在发育中的海马区和成年海马区均有表达。Western blotting和免疫组织化学显示SK2蛋白随年龄增加而增加。伴随而来的是亚细胞定位的转变。发育早期(P5)，SK2主要定位于锥体细胞层的内质网。但到了P30，SK2几乎只在树突和棘中表达。在发育过程中，突触后密度(PSD)处的SK2水平也有所增加。在成人，SK2在脊柱质膜上的表达呈现从近端到远端的梯度。与SK2的这种重新分布和梯度一致，选择性SK通道阻滞剂阿帕明只增加了P15以上小鼠CA1区锥体神经元诱发的兴奋性突触后电位(EPSPS)。而阿帕明对近、远侧放射层突触和腔隙分子层突触的作用无明显差异。这些结果表明，含有SK2的通道表面表达在发育中增加和梯度，这是它们对神经传递的影响的基础，这可能有助于在早期发育期间增加记忆获得。
We investigated the temporal and spatial expression of SK2 in the developing mouse hippocampus using molecular and biochemical techniques, quantitative immunogold electron microscopy and electrophysiology. The mRNA encoding SK2 was expressed in the developing and adult hippocampus. Western blotting and immunohistochemistry showed that SK2 protein increased with age. This was accompanied by a shift in subcellular localization. Early in development (P5), SK2 was predominantly localized to the endoplasmic reticulum in the pyramidal cell layer. But by P30 SK2 was almost exclusively expressed in the dendrites and spines. The level of SK2 at the postsynaptic density (PSD) also increased during development. In the adult, SK2 expression on the spine plasma membrane showed a proximal-to-distal gradient. Consistent with this redistribution and gradient of SK2, the selective SK channel blocker apamin increased evoked excitatory postsynaptic potentials (EPSPs) only in CA1 pyramidal neurons from mice older than P15. However, the effect of apamin on EPSPs was not different between synapses in proximal or distal stratum radiatum or stratum lacunosum-moleculare in adult. These results show a developmental increase and gradient in SK2-containing channel surface expression that underlie their influence on neurotransmission, and that may contribute to increased memory acquisition during early development.
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