Developmental regulation of the neuronal-specific isoform of K-Cl cotransporter KCC2 in postnatal rat brains

Developmental regulation of the neuronal-specific isoform of K-Cl cotransporter KCC2 in postnatal rat brains
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DOI:
10.1002/(sici)1097-4695(19990615)39:4
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发表时间:
1999-06-15
期刊:
JOURNAL OF NEUROBIOLOGY
影响因子:
--
通讯作者:
Delpire, E
Delpire, E
中科院分区:
其他
文献类型:
--
作者:
Lu, J;Karadsheh, M;Delpire, E

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我们研究了KCC 2亚型的K-CI协同转运蛋白在发育和成人大脑中的表达,使用针对KCC 2蛋白的独特区域的亲和纯化抗体。显示表达仅限于海马和小脑中的细胞体和细胞突起处的神经元。在起源于CA 1锥体细胞的突起末端表达似乎最高。通过北方和Western印迹分析,在整个大鼠脑中,以及通过免疫荧光在海马中,证明了KCC 2表达的发育上调。KCC 2的表达水平在出生时是最低的,在出生后的发育过程中显着增加。这种表达模式与Na-K-2Cl协同转运蛋白的表达模式相反,后者在未成熟的大脑中高度表达,并在发育过程中减少。Ii-Cl协同转运蛋白表达的上调与神经元细胞内Cl-浓度的发育性下调一致。细胞内Cl-的水平,反过来,决定兴奋与抑制反应的神经递质γ-氨基丁酸在未成熟与成熟的大脑。最后,在背根神经节神经元中显示KCC 2表达,表明协同转运蛋白的表达并不严格限于中枢神经系统神经元。(C)John Wiley & Sons,Inc.
We examined the expression of the KCC2 isoform of the K-CI cotransporter in the developing and adult brain, using an affinity-purified antibody directed against a unique region of the KCC2 protein. Expression was shown to be limited to neurons at the cell bodies and cell processes in the hippocampus and cerebellum. Expression seemed to be the highest at the end of processes that originated from the CA1 pyramidal cells. Developmental up-regulation of KCC2 expression was demonstrated in the entire rat brain by Northern and Western blot analyses, and in the hippocampus by immunofluorescence. Level of KCC2 expression was minimal at birth and increased significantly during postnatal development. This pattern of expression was opposite to the one of the Na-K-2Cl cotransporter that Is highly expressed in immature brain and decreases during development. The up-regulation of the Ii-CI cotransporter expression is consistent Kith the developmental down-regulation of the intracellular Cl- concentration in neurons. The level of intracellular Cl-, in turn, determines the excitatory versus inhibitory response of the neurotransmitter gamma-aminobutyric acid in the immature versus mature brain. Finally KCC2 expression was shown In dorsal root ganglion neurons, demonstrating that expression of the cotransporter is not strictly confined to central nervous system neurons. (C) 1999 John Wiley & Sons, Inc.