title: Human nongastric H+-K+-ATPase: transport properties of ATP1al1 assembled with different beta-subunits.
abstract: To investigate whether nongastric H+-K+-ATPases transport Na+ in exchange for K+ and whether different beta-isoforms influence their transport properties, we compared the functional properties of the catalytic subunit of human nongastric H+-K+-ATPase, ATP1al1 (AL1), and of the Na+-K+-ATPase alpha1-subunit (alpha1) expressed in Xenopus oocytes, with different beta-subunits. Our results show that betaHK and beta1-NK can produce functional AL1/beta complexes at the oocyte cell surface that, in contrast to alpha1/beta1 NK and alpha1/betaHK complexes, exhibit a similar apparent K+ affinity. Similar to Na+-K+-ATPase, AL1/beta complexes are able to decrease intracellular Na+ concentrations in Na+-loaded oocytes, and their K+ transport depends on intra- and extracellular Na+ concentrations. Finally, controlled trypsinolysis reveals that beta-isoforms influence the protease sensitivity of AL1 and alpha1 and that AL1/beta complexes, similar to the Na+-K+-ATPase, can undergo distinct K+-Na+- and ouabain-dependent conformational changes. These results provide new evidence that the human nongastric H+-K+-ATPase interacts with and transports Na+ in exchange for K+ and that beta-isoforms have a distinct effect on the overall structural integrity of AL1 but influence its transport properties less than those of the Na+-K+-ATPase alpha-subunit.
authors.affiliation: Institute Of Pharmacology And Toxicology of The University, CH-1005 Lausanne, Switzerland.
authors.forename: Gilles
authors.initials: G
authors.lastname: Crambert
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Horisberger
authors.forename: Nikolai N
authors.initials: NN
authors.lastname: Modyanov
authors.forename: Käthi
authors.initials: K
authors.lastname: Geering
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017506:H(+)-K(+)-Exchanging ATPase / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008024:Ligands; D008968:Molecular Conformation; D009865:Oocytes; D010042:Ouabain / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D014981:Xenopus
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008024:Ligands; D010042:Ouabain; D010447:Peptide Hydrolases; C088641:ATP12A protein, human; D017506:H(+)-K(+)-Exchanging ATPase; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium