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来自人类神经内分泌细胞的河豚毒素敏感性电压激活钠通道家族新成员的结构与功能表达

Structure and functional expression of a new member of the tetrodotoxin-sensitive voltage-activated sodium channel family from human neuroendocrine cells.

作者信息

Klugbauer N, Lacinova L, Flockerzi V, Hofmann F

机构信息

Institut für Pharmakologie und Toxikologie Technischen Universität München, Germany.

出版信息

EMBO J. 1995 Mar 15;14(6):1084-90. doi: 10.1002/j.1460-2075.1995.tb07091.x.

DOI:10.1002/j.1460-2075.1995.tb07091.x
PMID:7720699
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC398185/
Abstract

A member of a new subclass of the voltage-activated sodium channel genes has been cloned from the human medullary thyroid carcinoma (hMTC) cell line. The cDNA of hNE-Na (human neuroendocrine sodium channel) encodes a 1977 amino acid protein which phylogenetically represents a link between sodium channels isolated from skeletal muscle and brain. The hNE-Na alpha subunit was transiently expressed in human embryonic kidney cells either alone or in combination with the human sodium channel beta 1 subunit. The channel exhibited rapid activation and inactivation kinetics, and was blocked by tetrodotoxin and cadmium with IC50 values of 24.5 nM and 1.1 mM, respectively. Action potentials were generated in cells expressing high levels of hNE-Na. Northern blot and reverse transcription-polymerase chain reaction (RT-PCR) analyses demonstrated its expression in hMTC cells, in a C-cell carcinoma, and in thyroid and adrenal gland. Transcripts were not identified in pituitary gland, brain, heart, liver or kidney, indicating that the hNE-Na is a sodium channel solely expressed in neuroendocrine cells.

摘要

从人甲状腺髓样癌(hMTC)细胞系中克隆出了电压激活钠通道基因新亚类的一个成员。hNE-Na(人神经内分泌钠通道)的cDNA编码一种1977个氨基酸的蛋白质,从系统发育角度来看,它代表了从骨骼肌和脑中分离出的钠通道之间的一种联系。hNE-Naα亚基单独或与人钠通道β1亚基共同在人胚肾细胞中瞬时表达。该通道表现出快速激活和失活动力学,并且分别被河豚毒素和镉阻断,IC50值分别为24.5 nM和1.1 mM。在高表达hNE-Na的细胞中产生了动作电位。Northern印迹和逆转录-聚合酶链反应(RT-PCR)分析表明它在hMTC细胞、一种C细胞癌以及甲状腺和肾上腺中表达。在垂体、脑、心脏、肝脏或肾脏中未鉴定出转录本,这表明hNE-Na是一种仅在神经内分泌细胞中表达的钠通道。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24f4/398185/51a6d6401ba2/emboj00030-0042-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24f4/398185/51a6d6401ba2/emboj00030-0042-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24f4/398185/51a6d6401ba2/emboj00030-0042-a.jpg

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