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编码低电压激活(T型)钙通道的基因家族中三个成员的差异分布。

Differential distribution of three members of a gene family encoding low voltage-activated (T-type) calcium channels.

作者信息

Talley E M, Cribbs L L, Lee J H, Daud A, Perez-Reyes E, Bayliss D A

机构信息

Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA.

出版信息

J Neurosci. 1999 Mar 15;19(6):1895-911. doi: 10.1523/JNEUROSCI.19-06-01895.1999.

Abstract

Low voltage-activated (T-type) calcium currents are observed in many central and peripheral neurons and display distinct physiological and functional properties. Using in situ hybridization, we have localized central and peripheral nervous system expression of three transcripts (alpha1G, alpha1H, and alpha1I) of the T-type calcium channel family (CaVT). Each mRNA demonstrated a unique distribution, and expression of the three genes was largely complementary. We found high levels of expression of these transcripts in regions associated with prominent T-type currents, including inferior olivary and thalamic relay neurons (which expressed alpha1G), sensory ganglia, pituitary, and dentate gyrus granule neurons (alpha1H), and thalamic reticular neurons (alpha1I and alpha1H). Other regions of high expression included the Purkinje cell layer of the cerebellum, the bed nucleus of the stria terminalis, the claustrum (alpha1G), the olfactory tubercles (alpha1H and alpha1I), and the subthalamic nucleus (alpha1I and alpha1G). Some neurons expressed high levels of all three genes, including hippocampal pyramidal neurons and olfactory granule cells. Many brain regions showed a predominance of labeling for alpha1G, including the amygdala, cerebral cortex, rostral hypothalamus, brainstem, and spinal cord. Exceptions included the basal ganglia, which showed more prominent labeling for alpha1H and alpha1I, and the olfactory bulb, the hippocampus, and the caudal hypothalamus, which showed more even levels of all three transcripts. Our results are consistent with the hypothesis that differential gene expression underlies pharmacological and physiological heterogeneity observed in neuronal T-type calcium currents, and they provide a molecular basis for the study of T-type channels in particular neurons.

摘要

在许多中枢和外周神经元中可观察到低电压激活(T型)钙电流,且其表现出独特的生理和功能特性。利用原位杂交技术,我们已经定位了T型钙通道家族(CaVT)的三种转录本(α1G、α1H和α1I)在中枢和外周神经系统中的表达。每种mRNA都显示出独特的分布,并且这三个基因的表达在很大程度上是互补的。我们发现这些转录本在与显著T型电流相关的区域有高水平表达,包括下橄榄核和丘脑中继神经元(表达α1G)、感觉神经节、垂体以及齿状回颗粒神经元(α1H),还有丘脑网状神经元(α1I和α1H)。其他高表达区域包括小脑浦肯野细胞层、终纹床核、屏状核(α1G)、嗅结节(α1H和α1I)以及底丘脑核(α1I和α1G)。一些神经元表达所有三个基因的高水平,包括海马锥体细胞和嗅颗粒细胞。许多脑区显示α1G标记占优势,包括杏仁核、大脑皮层、下丘脑前部、脑干和脊髓。例外情况包括基底神经节,其显示α1H和α1I的标记更突出,以及嗅球、海马和下丘脑尾部,其显示所有三种转录本的水平更均匀。我们的结果与以下假设一致,即差异基因表达是神经元T型钙电流中观察到的药理学和生理学异质性的基础,并且它们为研究特定神经元中的T型通道提供了分子基础。

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