Molecular diversity of voltage-gated sodium channel alpha subunits expressed in neuronal and non-neuronal excitable cells
Molecular diversity of voltage-gated sodium channel alpha subunits expressed in neuronal and non-neuronal excitable cells
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DOI：
10.1016/j.neuroscience.2004.09.034
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发表时间：
2005-01-01
期刊：
影响因子：
3.3
通讯作者：
Valmier, J
中科院分区：
文献类型：
--
作者：
Mechaly, I;Scamps, F;Valmier, J
为了研究电压激活钠通道α亚基分子多样性在神经元和非神经元细胞兴奋性中的作用，我们采用膜片钳技术和单细胞RT-PCR技术对两种不同类型的哺乳动物可兴奋细胞（海马神经元和非神经元椭圆囊上皮毛细胞）进行了研究。在每种细胞类型中，尽管钠电流性质相似，但细胞与细胞之间存在多种不同的钠通道a亚基组合。mRNA亚型Nav1.2和Nav1.6是两种细胞类型中最常通过单细胞分析检测到的，而Nav1.3和Nav1.7也分别在胚胎海马神经元和新生儿椭圆囊毛细胞中适度表达。通过研究发生在小鼠直系同源物SCN 8A的外显子18处的Nav1.6的特定选择性剪接异构体，我们揭示了该亚基在不同的选择性剪接异构体下共存于两种细胞类型中。Nav1.6在椭圆囊上皮毛细胞中的非功能性亚型的表达排除了该亚基参与支持其兴奋性。因此，从功能的角度来看，本研究结果表明，在单细胞水平上，神经元和非神经元兴奋细胞表达不同的和复杂的模式的钠通道基因转录，但这种多样性本身不能解释这些细胞类型的钠电流特性。(C)2004年IBRO。由爱思唯尔有限公司出版。保留所有权利。
In order to investigate the role of molecular diversity of voltage-activated sodium channel alpha-subunits in excitability of neuronal and non-neuronal cells, we carried out patch-clamp recordings and single-cell RT-PCR on two different types of mammalian excitable cells i.e. hippocampal neurons and non-neuronal utricular epithelial hair cells. In each cell type, multiple different combinations of sodium channel a-subunits exist from cell to cell despite similar sodium current properties. The mRNA isoforms, Nav1.2 and Nav1.6, are the most frequently detected by single cell analysis in the two cell types while Nav1.3 and Nav1.7 are also moderately expressed in embryonic hippocampal neurons and in neonatal utricular hair cells respectively. By investigating the particular alternate splice isoforms of Nav1.6 occurring at the exon 18 of the mouse orthologue SCN8A, we revealed that this subunit co-exist in the two cell types under different alternative spliced isoforms. The expression of nonfunctional isoforms of Nav1.6 in utricular epithelial hair cells excludes the involvement of this subunit in supporting their excitability. Thus, from a functional point of view, the present results suggest that, at the single cell level, both neuronal and non-neuronal excitable cells expressed different and complex patterns of sodium channel gene transcripts but this diversity alone cannot explain the sodium current properties of these cell types. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.