The third sodium binding site of Na,K-ATPase is functionally linked to acidic pH-activated inward current.
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Li C, Geering K, Horisberger JD
The third sodium binding site of Na,K-ATPase is functionally linked to acidic pH-activated inward current.
J Membr Biol. 2006;213(1):1-9. Epub 2007 Mar 8.
- PubMed ID
- 17347782 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Potassium acetate Sodium/potassium-transporting ATPase subunit alpha-1 Protein Humans UnknownNot Available Details Potassium cation Sodium/potassium-transporting ATPase subunit alpha-1 Protein Humans UnknownNot Available Details Potassium sulfate Sodium/potassium-transporting ATPase subunit alpha-1 Protein Humans UnknownNot Available Details