Cloning and localization of the hyperpolarization-activated cyclic nucleotide-gated channel family in rat brain
Cloning and localization of the hyperpolarization-activated cyclic nucleotide-gated channel family in rat brain
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DOI：
10.1016/s0169-328x(00)00155-8
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发表时间：
2000-09-30
期刊：
影响因子：
--
通讯作者：
Nestler, EJ
中科院分区：
文献类型：
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作者：
Monteggia, LM;Eisch, AJ;Nestler, EJ
大脑和心脏中的节律性放电由起搏通道介导，起搏通道由超极化激活并由环核苷酸直接调节。最近的工作已经确定了一个新的基因家族，编码这样的通道，这被称为超极化激活，环核苷酸门控（HCN）通道。本文报道了HCN 1 -4的分子克隆及其在成年大鼠脑组织中的原位杂交定位。大鼠HCN 1 -4克隆显示与小鼠通道的推导的氨基酸序列的高度同源性（>97%同一性）。在成年人的大脑中的四个通道的mRNA表达进行了系统的评估，从嗅球到下脑干核。每种mRNA都表现出独特的分布模式。HCN 1表达在大脑皮质、海马、小脑和面部运动核中高度富集; HCN 2在乳头体、脑桥核、腹侧耳蜗核和斜方体核中高度丰富; NCN 3表达在下丘脑的视上核中最明显; HCN 4表达在内侧缰核和丘脑的前中继核和主中继核中最丰富。HCN通道的区域特异性的这些变化可以在整个脑系统中产生神经元起搏活性的重要差异。(C)2000 Elsevier Science B. V.保留所有权利。
Rhythmic firing in brain and heart is mediated by pacemaker channels that are activated by hyperpolarization and regulated directly by cyclic nucleotides. Recent work has identified a new gene family that encodes such channels, which are termed hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels. In this study, we report the molecular cloning and localization by in situ hybridization of HCN1-4 in adult rat brain. The rat HCN1-4 clones show high homology to the deduced amino acid sequence of the mouse channels (>97% identity). The mRNA expression of the four channels in adult brain was evaluated in a systematic manner from the olfactory bulb to lower brain stem nuclei. Each mRNA demonstrated a unique pattern of distribution. HCN1 expression is highly enriched in cerebral cortex, hippocampus, cerebellum, and facial motor nucleus; HCN2 is highly abundant in mamillary bodies, pontine nucleus, ventral cochlear nucleus, and nucleus of the trapezoid body; NCN3 expression is most pronounced in supraoptic nucleus of hypothalamus; and HCN4 expression is most abundant in medial habenula and anterior and principal relay nuclei of the thalamus. These variations in regional specificity of HCN channels could generate important differences in neuronal pacemaker activity across brain systems. (C) 2000 Elsevier Science B.V. All rights reserved.