title: Kinetic mechanism of inhibition of the Na+-pump and some of its partial reactions by external Na+ (Na+o).
abstract: The effects of external Na+ on the activity of the Na+-pump are complex. The first-order rate constant for Na+-efflux is reduced in the presence of very low external Na+ concentrations, and this inhibition is reversed when the Na+ level is raised. The same pattern has been observed for Na+-ATPase activity; however, it is not apparent from the current reaction mechanisms at which site (or sites) external Na+ binds to cause inhibition. In this paper, the effect of external Na+ on Na+-pump activity was studied by simulation, using a model similar to the Post-Albers scheme. Curves similar to those experimentally observed were obtained assuming that: (i) after phosphorylation, three Na+ ions are translocated and consecutively released to the external medium with decreasing dissociation constants; (ii) external Na+, with low affinity, binds to the K+o (external) sites stimulating dephosphorylation. These assumptions also permit one to explain the experimental observation that external Na+ (with both high and low affinities) competes with K+, inhibiting the K+ influx due to the Na+-pump, and the kinetically similar behavior of Na+-ATPase and ATP/ADP exchange reactions at low variable Na+ concentrations. The experimental evidence available that supports the present hypothesis is discussed.
authors.affiliation: Department of Physiology G4, University of Pennsylvania, Philadelphia 19104.
authors.forename: C H
authors.initials: CH
authors.lastname: Pedemonte
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D003864:Depression, Chemical; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D012964:Sodium / Q000493:pharmacokinetics*; D015222:Sodium Channels / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D015222:Sodium Channels; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase