The heterotetrameric architecture of the epithelial sodium channel (ENaC)

被引:328
作者
Firsov, D [1 ]
Gautschi, I [1 ]
Merillat, AM [1 ]
Rossier, BC [1 ]
Schild, L [1 ]
机构
[1] Univ Lausanne, Inst Pharmacol & Toxicol, CH-1005 Lausanne, Switzerland
关键词
amiloride; channel pore; ENaC; epithelial sodium channel; subunit stoichiometry;
D O I
10.1093/emboj/17.2.344
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The epithelial sodium channel (ENaC) is a key element for the maintenance of sodium balance and the regulation of blood pressure, Three homologous ENaC subunits (alpha, beta and gamma) assemble to form a highly Na+- selective channel, However, the subunit stoichiometry of ENaC has not yet been solved, Quantitative analysis of cell surface expression of ENaC alpha, beta and gamma subunits shows that they assemble according to a fixed stoichiometry, with alpha ENaC as the most abundant subunit, Functional assays based on differential sensitivities to channel blockers elicited by mutations tagging each a, beta and gamma subunit are consistent with a four subunit stoichiometry composed of two alpha, one beta and one gamma, Expression of concatameric cDNA constructs made of different combinations of ENaC subunits confirmed the four subunit channel stoichiometry and showed that the arrangement of the subunits around the channel pore consists of two alpha subunits separated by beta and gamma subunits.
引用
收藏
页码:344 / 352
页数:9
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