The third sodium binding site of Na,K-ATPase is functionally linked to acidic pH-activated inward current

Details

Ressource 1Download: REF.pdf (324.36 [Ko])
State: Public
Version: Final published version
License: Not specified
It was possible to publish this article open access thanks to a Swiss National Licence with the publisher.
Serval ID
serval:BIB_EA2DCBF6C5B9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The third sodium binding site of Na,K-ATPase is functionally linked to acidic pH-activated inward current
Journal
Journal of Membrane Biology
Author(s)
Li  C., Geering  K., Horisberger  J. D.
ISSN
0022-2631 (Print)
Publication state
Published
Issued date
2006
Volume
213
Number
1
Pages
1-9
Notes
In Vitro
Journal Article
Research Support, Non-U.S. Gov't
Abstract
Sodium- and potassium-activated adenosine triphosphatases (Na,K-ATPase) is the ubiquitous active transport system that maintains the Na(+) and K(+) gradients across the plasma membrane by exchanging three intracellular Na(+) ions against two extracellular K(+) ions. In addition to the two cation binding sites homologous to the calcium site of sarcoplasmic and endoplasmic reticulum calcium ATPase and which are alternatively occupied by Na(+) and K(+) ions, a third Na(+)-specific site is located close to transmembrane domains 5, 6 and 9, and mutations close to this site induce marked alterations of the voltage-dependent release of Na(+) to the extracellular side. In the absence of extracellular Na(+) and K(+), Na,K-ATPase carries an acidic pH-activated, ouabain-sensitive "leak" current. We investigated the relationship between the third Na(+) binding site and the pH-activated current. The decrease (in E961A, T814A and Y778F mutants) or the increase (in G813A mutant) of the voltage-dependent extracellular Na(+) affinity was paralleled by a decrease or an increase in the pH-activated current, respectively. Moreover, replacing E961 with oxygen-containing side chain residues such as glutamine or aspartate had little effect on the voltage-dependent affinity for extracellular Na(+) and produced only small effects on the pH-activated current. Our results suggest that extracellular protons and Na(+) ions share a high field access channel between the extracellular solution and the third Na(+) binding site.
Keywords
Amino Acid Substitution Animals Binding Sites Female Hydrogen-Ion Concentration Membrane Potentials Models, Biological Mutagenesis, Site-Directed Na(+)-K(+)-Exchanging ATPase/chemistry/genetics/*metabolism Oocytes/metabolism Ouabain/pharmacology Potassium/metabolism Protein Structure, Tertiary Rats Recombinant Proteins/chemistry/genetics/metabolism Sodium/metabolism Xenopus
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 12:28
Last modification date
14/02/2022 7:57
Usage data