A new subunit of the epithelial Na+ channel identifies regions involved in Na+ self-inhibition

43Citations
Citations of this article
36Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

The epithelial Na+ channel (ENaC) is the apical entry pathway for Na+ in many Na+-reabsorbing epithelia. ENaC is a heterotetrameric protein composed of homologous α, β, and γ subunits. Mutations in ENaC cause severe hypertension or salt wasting in humans; and consequently, ENaC activity is tightly controlled. According to the concept of Na+ self-inhibition, the extracellular Na+ ion itself can reduce ENaC activity. The molecular basis for Na+ self-inhibition is unknown. Here, we describe cloning of a new ENaC subunit from Xenopus laevis (εxENaC). εxENaC can replace αxENaC and formed functional, highly selective, amiloride-sensitive Na+ channels when coexpressed with βxENaC and γxENaC. Channels containing εxENaC showed strong inhibition by extracellular Na+. This Na+ self-inhibition was significantly slower than for αxENaC-containing channels. Using site-directed mutagenesis, we show that the proximal part of the large extracellular domain controls the speed of self-inhibition. This suggests that this region is involved in conformational changes during Na+ self-inhibition.

References Powered by Scopus

Amiloride-sensitive epithelial Na<sup>+</sup> channel is made of three homologous subunits

1837Citations
N/AReaders
Get full text

Epithelial sodium channels: Function, structure and regulation

1063Citations
N/AReaders
Get full text

The heterotetrameric architecture of the epithelial sodium channel (ENaC)

375Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Furin cleavage activates the epithelial Na<sup>+</sup> channel by relieving Na<sup>+</sup> self-inhibition

144Citations
N/AReaders
Get full text

Epithelial Na<sup>+</sup> Channels Are Activated by Laminar Shear Stress

140Citations
N/AReaders
Get full text

ENaC structure and function in the wake of a resolved structure of a family member

119Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Babini, E., Geisler, H. S., Siba, M., & Gründer, S. (2003). A new subunit of the epithelial Na+ channel identifies regions involved in Na+ self-inhibition. Journal of Biological Chemistry, 278(31), 28418–28426. https://doi.org/10.1074/jbc.M301315200

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 7

50%

Researcher 4

29%

Professor / Associate Prof. 3

21%

Readers' Discipline

Tooltip

Agricultural and Biological Sciences 11

55%

Biochemistry, Genetics and Molecular Bi... 7

35%

Medicine and Dentistry 1

5%

Engineering 1

5%

Save time finding and organizing research with Mendeley

Sign up for free