Molecular cloning, functional expression and chromosomal localization of an amiloride-sensitive Na+ channel from human small intestine
Molecular cloning, functional expression and chromosomal localization of an amiloride-sensitive Na+ channel from human small intestine
复制标题
DOI：
10.1016/s0014-5793(00)01403-4
复制
发表时间：
2000-04-14
期刊：
影响因子：
3.5
通讯作者：
Lingueglia, E
中科院分区：
文献类型：
--
作者：
Schaefer, L;Sakai, H;Lingueglia, E
amiloride敏感的Na+通道属于最近发现的NaC/DEG基因家族，在包括上皮和中枢和外周神经元在内的几种人体组织中被发现。我们在这里描述了编码一个非cl人amiloride敏感的Na+通道亚基的cDNA的分子克隆，该亚基主要在小肠中表达，被称为hINaC（人肠Na+通道）。该蛋白与最近发现的啮齿动物通道BLINaC相似，与酸感应离子通道（asic）相对接近（氨基酸同源性分别为79%和29%）。asic被细胞外质子激活，可能参与与组织酸中毒相关的感觉神经元的伤害感受，hINaC不是通过降低外部pll激活的，而是通过引入功能获得突变来激活，并在爪蟾卵母细胞中表达时揭示了一个重要的Na+通道活性，该活性被阿米洛利阻断（IC50 = 0.5 μ M）。这些结果表明存在一种未知的hnaac生理激活剂（如细胞外配体），这种新的阿米洛胺敏感Na+通道在人小肠中的存在可能具有有趣的生理和病理生理意义，仍有待澄清。点突变对该通道的大量激活可能与先前在线虫机械敏感神经元中表达的通道中观察到的变性素样行为有关。hINaC基因已被定位在人类基因组的4q31.3-q32区域，(C) 2000年欧洲生化学会联合会。
Amiloride-sensitive Na+ channels belonging to the recently discovered NaC/DEG family of genes have been found in several human tissues including epithelia and central and peripheral neurons, We describe here the molecular cloning of a cDNA encoding a nor cl human amiloride-sensitive Na+ channel subunit that is principally expressed in the small intestine and has been called hINaC (human intestine Na+ channel), This protein is similar to the recently identified rodent channel BLINaC and is relatively close to the acid sensing ion channels (ASICs) (79 and 29%, amino acid identity, respectively). ASICs are activated by extracellular protons and probably participate in sensory neurons to nociception linked to tissue acidosis, hINaC is not activated by lowering the external pll but gain-of-function mutations call he introduced and reveal when expressed in Xenopus oocytes, an important Na+ channel activity which is blocked by amiloride (IC50 = 0.5 mu M). These results suggest the existence of a still unknown physiological activator for hINaC (e.g. an extracelluar ligand), The presence of this new amiloride-sensitive Na+ channel in human small intestine probably has interesting physiological as well as physiopathological implications that remain to he clarified. The large activation of this channel by point mutations may be associated,vith a degenerin-like behavior as previously observed for channels expressed in nematode mechanosensitive neurons. The hINaC gene has been mapped on the 4q31.3-q32 region of the human genome, (C) 2000 Federation of European Biochemical Societies.