This work was supported by a grant from The Department of Education of Liaoning Province (05L500).
Nav1.5电压-门控钠通道 (VGSC) 被认为是心肌的特异性通道,但最近的研究发现,该通道在脑组织尤其是边缘系统中亦广泛分布. 此前,在对人神经母细胞瘤细胞钠通道的基因克隆中,发现Nav1.5/SCN5A基因的第6A外显子参与编码该通道. 采用人及鼠脑组织,通过RT-PCR法对Nav1.5钠通道基因进行克隆发现:Nav1.5/SCN5A基因中的第6A外显子参与编码了该通道,而心肌等其他组织却是第6外显子参与编码该通道. 人Nav1.5/SCN5A基因的第6A 和第6外显子都定位于3号染色体,共有92个碱基,都可以编码产生30个氨基酸,但却有7个氨基酸不同. 人和鼠脑组织Nav1.5/SCN5A基因的第6A外显子仅有一个碱基不同,却产生相同的氨基酸序列. RT-PCR法证实第6A外显子在鼠脑的不同部位表达不同, 第6外显子在大鼠不同组织中的表达也不同,这为深入研究不同系统中Nav1.5钠通道的功能提供了基础.
Among the tetrodotoxin-resistant(TTX-R) α-subunits, Nav1.5 mRNA showed the strongest expression in the heart, according with its consideration as the cardiac Na+ channel. Compared to its mRNA transcription in the heart, the Nav1.5/SCN5A gene was also expressed in high levels in the brain, especially limbic regions of the brain. Exon6A of Nav1.5/SCN5A gene was first found in cloning of Nav1.5 channel in human neuroblastoma cells. It was found that it is exon6A that encodes Nav1.5 channels in human and rat brain while it is exon6 that encodes Nav1.5 channels in other tissues in the cloning of Nav1.5 channel in these tissues, Both exon6A and exon6 have 92 base pairs, which encodes 30 amino acid residues, and are located in human chromosome 3. But these two resulting products differ by 7 amino acid residues. There is only one different base pair between the enon6As encoding Nav1.5 channels in human and rat brain, but their encoding amino acid residues are identical. The expressions of exon6A in different part of the brain are different and the similar result was found in the expressions of exon6 among different tissues of rat when detected by using RT-PCR method. The study is useful for making further investigation in the functional analysis of Nav1.5 channels in different tissues.
王军,宗志红,欧绍武,王运杰,任成涛,林 毅,孟晓娜.编码脑组织Nav1.5钠通道新外显子的克隆、鉴定和分布[J].生物化学与生物物理进展,2007,34(3):255-259
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