Differential and age-dependent expression of hyperpolarization-activated, cyclic nucleotide-gated cation channel isoforms 1-4 suggests evolving roles in the developing rat hippocampus
Differential and age-dependent expression of hyperpolarization-activated, cyclic nucleotide-gated cation channel isoforms 1-4 suggests evolving roles in the developing rat hippocampus
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DOI：
10.1016/s0306-4522(01)00314-1
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发表时间：
2001-01-01
期刊：
影响因子：
3.3
通讯作者：
Baram, TZ
中科院分区：
文献类型：
--
作者：
Bender, RA;Brewster, A;Baram, TZ
超极化激活阳离子电流(I-h)存在于包括丘脑和海马区在内的几个脑区。这些电流在促进同步化网络活动和决定神经细胞膜特性方面的重要功能已经逐渐被认识到，但这些电流的分子基础才刚刚出现。I-h电流是由超极化激活的环核苷酸门控阳离子通道(HCN)产生的。这些通道蛋白由至少四个HCN基因编码，这些基因控制着所产生的通道的动力学和功能特性。鉴于i-h介导的协调神经元活动对功能海马网成熟的潜在影响，本研究从区域和单细胞水平研究了HCN基因家族的四个成员在出生后海马发育过程中的表达。这些实验结果表明，HCN 1、2和4在大鼠海马结构的神经元间和主细胞群中存在差异表达。每种HCN亚型的表达谱在出生后发育过程中发生演变，在出生后早期观察到的模式与成熟海马区的模式显著不同。HCN在海马区的表达先于齿状回，提示HCN介导的起搏活动可能先于门区在海马区产生。综上所述，这些发现表明在不同的海马区细胞群中特定的HCN表达具有年龄依赖性的时空演化，并提示这些通道在海马协调活动的成熟过程中起着不同和进化的作用。(C)2001年IBRO。爱思唯尔科学有限公司出版。版权所有。
Hyperpolarization-activated cation currents (I-h) are found in several brain regions including thalamus and hippocampus. Important functions of these currents in promoting synchronized network activity and in determining neuronal membrane properties have been progressively recognized, but the molecular underpinnings of these currents are only emerging. I-h currents are generated by hyperpolarization-activated, cyclic nucleotide-gated cation channels (HCNs). These channel proteins are encoded by at least four HCN genes, that govern the kinetic and functional properties of the resulting channels. Because of the potential impact of I-h-mediated coordinated neuronal activity on the maturation of the functional hippocampal network, this study focused on determining the expression of the four members of the HCN gene family throughout postnatal hippocampal development at both the regional and single cell level.The results of these experiments demonstrated that HCNs 1, 2 and 4 are differentially expressed in interneuronal and principal cell populations of the rat hippocampal formation. Expression profiles of each HCN isoform evolve during postnatal development, and patterns observed during early postnatal ages differ significantly from those in mature hippocampus. The onset of HCN expression in interneurons of the hippocampus proper precedes that in the dentate gyrus, suggesting that HCN-mediated pacing activity may be generated in hippocampal interneurons prior to those in the hilus.Taken together, these findings indicate an age-dependent spatiotemporal evolution of specific HCN expression in distinct hippocampal cell populations, and suggest that these channels serve differing and evolving functions in the maturation of coordinated hippocampal activity. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.