BASIC-a bile acid-sensitive ion channel highly expressed in bile ducts
BASIC-a bile acid-sensitive ion channel highly expressed in bile ducts
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DOI：
10.1096/fj.12-207043
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发表时间：
2012-10-01
期刊：
影响因子：
4.8
通讯作者：
Gruender, Stefan
中科院分区：
文献类型：
--
作者：
Wiemuth, Dominik;Sahin, Hacer;Gruender, Stefan
脑肝肠Na+通道（BLINaC）是DEG/ENaC基因家族的一个功能未知的离子通道。来自大鼠（rBLINaC）和人类（INaC）的BLINaC在休息时是无活性的，其激活模式仍不清楚。在这里，我们发现BLINaC蛋白定位于胆管细胞，胆管上皮细胞。此外，我们提供的证据表明，rBLINaC和INaC被胆汁酸，特别是鹅去氧胆酸和猪去氧胆酸（EC 50 =2.1 +/- 0.05 mM）强烈激活。因此，BLINaC似乎是对胆汁酸的生理浓度敏感的胆管的上皮阳离子通道。BLINaC与酸敏感离子通道（ASIC）和上皮Na+通道（ENaC）相关，并与ASIC共享配体激活，与ENaC共享上皮定位。因此，基于BLINaC与ASIC的密切同源性及其被胆汁酸激活，我们建议将BLINaC重命名为胆汁酸敏感离子通道（BASIC）。Wiemuth，D.，Sahin，H.，法尔肯伯格，B。H、勒菲弗尔角M. T.，Wasteland，H. E、Grunder，S. BASIC-一种在胆管中高度表达的胆汁酸敏感离子通道。FASEB J.26，4122-4130（2012）。www.fasebj.org
Brain liver intestine Na+ channel (BLINaC) is an ion channel of the DEG/ENaC gene family of unknown function. BLINaC from rats (rBLINaC) and humans (INaC) is inactive at rest, and its mode of activation has remained unclear. Here, we show that the BLINaC protein localizes to cholangiocytes, epithelial cells that line bile ducts. Moreover, we provide evidence that rBLINaC and INaC are robustly activated by bile acids, in particular chenodeoxycholic acid and hyodeoxycholic acid (EC50 =2.1 +/- 0.05 mM). Thus, BLINaC appears to be an epithelial cation channel of bile ducts sensitive to physiological concentrations of bile acids. BLINaC is related to acid-sensing ion channels (ASICs) and to the epithelial Na+ channel (ENaC) and shares ligand activation with ASICs and epithelial localization with ENaC. Therefore, based on the close homology of BLINaC to ASICs and its activation by bile acids, we propose to rename BLINaC bile acid-sensitive ion channel (BASIC).-Wiemuth, D., Sahin, H., Falkenburger, B. H., Lefevre, C. M. T., Wasmuth, H. E., Grunder, S. BASIC-a bile acid-sensitive ion channel highly expressed in bile ducts. FASEB J. 26, 4122-4130 (2012). www.fasebj.org