title: Kinetic comparisons of heart and kidney Na+,K(+)-ATPases.
abstract: Most kinetic measurements of the partial reactions of Na(+),K(+)-ATPase have been conducted on enzyme from mammalian kidney. Here we present a kinetic model that is based on the available equilibrium and kinetic parameters of purified kidney enzyme, and allows predictions of its steady-state turnover and pump current in intact cells as a function of ion and ATP concentrations and the membrane voltage. Using this model, we calculated the expected dependence of the pump current on voltage and extracellular Na(+) concentration. The simulations indicate a lower voltage dependence at negative potentials of the kidney enzyme in comparison with heart muscle Na(+),K(+)-ATPase, in agreement with experimental results. The voltage dependence is enhanced at high extracellular Na(+) concentrations. This effect can be explained by a voltage-dependent depopulation of extracellular K(+) ion binding sites on the E2P state and an increase in the proportion of enzyme in the E1P(Na(+))(3) state in the steady state. This causes a decrease in the effective rate constant for occlusion of K(+) by the E2P state and hence a drop in turnover. Around a membrane potential of zero, negligible voltage dependence is observed because the voltage-independent E2(K(+))(2) → E1 + 2K(+) transition is the major rate-determining step.
authors.affiliation: Department of Cardiology, Royal North Shore Hospital, and Kolling Institute, University of Sydney, Sydney, Australia.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Garcia
authors.forename: Helge H
authors.initials: HH
authors.lastname: Rasmussen
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Apell
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Clarke
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D015971:Gene Expression Regulation, Enzymologic; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000201:enzymology*; D009928:Organ Specificity; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry / Q000378:metabolism*; D029867:Xenopus Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D029867:Xenopus Proteins; D000254:Sodium-Potassium-Exchanging ATPase