Influx of Calcium Through L-Type Calcium Channels in Early Postnatal Regulation of Chloride Transporters in the Rat Hippocampus
Influx of Calcium Through L-Type Calcium Channels in Early Postnatal Regulation of Chloride Transporters in the Rat Hippocampus
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DOI：
10.1002/dneu.20749
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发表时间：
2009-11-01
影响因子：
3
通讯作者：
Mynlieff, Michelle
中科院分区：
文献类型：
--
作者：
Bray, Jennifer G.;Mynlieff, Michelle
在出生后早期，GABA（B）受体激活易化大鼠海马L型钙电流。L型电流可能调节的一个发育过程是K+Cl-共转运蛋白（KCC 2）和N（+）K（+）2Cl（-）共转运蛋白（NKCC 1）表达的变化，它们参与GABA能系统的成熟。本研究探讨了L型电流，GABA（B）受体，氯转运蛋白的表达在发育过程中之间的联系。GABA（B）受体对L型电流的易化作用在发育的第二周更为显著，在从7日龄大鼠分离的培养物中表现出易化作用的细胞百分比最高（37.5%）。研究KCC 2和NKCC 1的蛋白水平以确定表达的发育时程以及用L型通道拮抗剂和GABA（B）受体激动剂处理后的表达。培养的两种氯转运蛋白的时间过程模拟了从不同年龄分离的海马组织中观察到的。KCC 2水平在出生后的前两周急剧增加，而NKCC 1保持相对稳定，这表明氯转运蛋白的比例在介导氯逆转电位的发育变化中是重要的。用L型拮抗剂尼莫地平处理培养物不影响NKCC 1的蛋白水平，但在出生后第一周显著降低了KCC 2的上调。此外，钙电流易化发生在KCC 2表达大幅增加之前。这些结果表明，KCC 2的表达在出生后早期的海马神经元通过L-型通道的钙内流调节。(C)2009 Wiley Periodicals，Inc. Develop Neurobiol 69：885-896. 2009
During the early postnatal period, GABA(B) receptor activation facilitates L-type calcium current in rat hippocampus. One developmental process that L-type current may regulate is the change in expression of the K+Cl- co-transporter (KCC2) and N(+)K(+)2Cl(-) co-transporter (NKCC1), which are involved in the maturation of the GABAergic system. The present study investigated the connection between L-type current, GABA(B) receptors, and expression of chloride transporters during development. The facilitation of L-type current by GABA(B) receptors is more prominent in the second week of development, with the highest percentage of cells exhibiting facilitation in cultures isolated from 7 day old rats (37.5%). The protein levels of KCC2 and NKCC1 were investigated to determine the developmental timecourse of expression as well as expression following treatment with an L-type channel antagonist and a GABA(B) receptor agonist. The time course of both chloride transporters in culture mimics that seen in hippocampal tissue isolated from various ages. KCC2 levels increased drastically in the first two postnatal weeks while NKCC1 remained relatively stable, suggesting that the ratio of the chloride transporters is important in mediating the developmental change in chloride reversal potential. Treatment of cultures with the L-type antagonist nimodipine did not affect protein levels of NKCC1, but significantly decreased the upregulation of KCC2 during the first postnatal week. In addition, calcium current facilitation occurs slightly before the large increase in KCC2 expression. These results suggest that the expression of KCC2 is regulated by calcium influx through L-type channels in the early postnatal period in hippocampal neurons. (C) 2009 Wiley Periodicals, Inc. Develop Neurobiol 69: 885-896. 2009