ArticleThe Journal of general physiology2000
Gating induces a conformational change in the outer vestibule of ENaC.
Article in The Journal of general physiology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- Analysis of sodium self-inhibition of the epithelial sodium channel (ENaC) using classical and medium-throughput automated two-electrode voltage-clamp recordings.Pflugers Archiv : European journal of physiology · 2026Article
- Guinea pig δβγ-ENaC is locked in an open state and uncoupled from regulation by proteases.Pflugers Archiv : European journal of physiology · 2026Article
- Bile acids regulate the epithelial NaThe Journal of physiology · 2022Article
- Transmembrane serine protease 2 (TMPRSS2) proteolytically activates the epithelial sodium channel (ENaC) by cleaving the channel's γ-subunit.The Journal of biological chemistry · 2022Article
- Accessibility of ENaC extracellular domain central core residues.The Journal of biological chemistry · 2022Article
- Thumb domains of the three epithelial NaThe Journal of biological chemistry · 2018Article
- The N terminus of α-ENaC mediates ENaC cleavage and activation by furin.The Journal of general physiology · 2018Article
- Pore-lining residues of MEC-4 and MEC-10 channel subunits tune theThe Journal of biological chemistry · 2018Article
- Incorporation of the δ-subunit into the epithelial sodium channel (ENaC) generates protease-resistant ENaCs inThe Journal of biological chemistry · 2018Article
- Restoration of Epithelial Sodium Channel Function by Synthetic Peptides in Pseudohypoaldosteronism Type 1B Mutants.Frontiers in pharmacology · 2017Article
- Activation of the Human Epithelial Sodium Channel (ENaC) by Bile Acids Involves the Degenerin Site.The Journal of biological chemistry · 2016Article
- ENaC in the Rabbit Lacrimal Gland and its Changes During Sjögren Syndrome and Pregnancy.Eye & contact lens · 2015Article
- Intersubunit conformational changes mediate epithelial sodium channel gating.The Journal of general physiology · 2014Article
- Electrostatic charge at position 552 affects the activation and permeation of FMRFamide-gated Na+ channels.The journal of physiological sciences : JPS · 2014Article
- Hypotonic regulation of mouse epithelial sodium channel in Xenopus laevis oocytes.The Journal of membrane biology · 2013Article
- Gamma subunit second transmembrane domain contributes to epithelial sodium channel gating and amiloride block.American journal of physiology. Renal physiology · 2013Article
- The genetic architecture of degenerin/epithelial sodium channels in Drosophila.G3 (Bethesda, Md.) · 2013Article
- Identification of extracellular domain residues required for epithelial Na+ channel activation by acidic pH.The Journal of biological chemistry · 2012Article
- Regulation of epithelial sodium channel trafficking by proprotein convertase subtilisin/kexin type 9 (PCSK9).The Journal of biological chemistry · 2012Article
- Contribution of residues in second transmembrane domain of ASIC1a protein to ion selectivity.The Journal of biological chemistry · 2012Article
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Abstract
The epithelial Na(+) channel (ENaC) is comprised of three homologous subunits (alpha, beta, and gamma). The channel forms the pathway for Na(+) absorption in the kidney, and mutations cause disorders of Na(+) homeostasis. However, little is known about the mechanisms that control the gating of ENaC. We investigated the gating mechanism by introducing bulky side chains at a position adjacent to the extracellular end of the second membrane spanning segment (549, 520, and 529 in alpha, beta, and gammaENaC, respectively). Equivalent "DEG" mutations in related DEG/ENaC channels in Caenorhabditis elegans cause swelling neurodegeneration, presumably by increasing channel activity. We found that the Na(+) current was increased by mutagenesis or chemical modification of this residue and adjacent residues in alpha, beta, and gammaENaC. This resulted from a change in the gating of ENaC; modification of a cysteine at position 520 in betaENaC increased the open state probability from 0. 12 to 0.96. Accessibility to this side chain from the extracellular side was state-dependent; modification occurred only when the channel was in the open conformation. Single-channel conductance decreased when the side chain contained a positive, but not a negative charge. However, alterations in the side chain did not alter the selectivity of ENaC. This is consistent with a location for the DEG residue in the outer vestibule. The results suggest that channel gating involves a conformational change in the outer vestibule of ENaC. Disruption of this mechanism could be important clinically since one of the mutations that increased Na(+) current (gamma(N530K)) was identified in a patient with renal disease.
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