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Branched reaction mechanism for the Na/K pump as an alternative explanation for a nonmonotonic currentvs. membrane potential response

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Summary

Nonmonotonic velocityvs. membrane potential curves are often taken as evidence that two steps involve charge movement through the electric field. However, a branched reaction scheme in which only one step involves charge movement per cycle can lead to a nonmonotonic response. A similar case occurs in enzyme kinetics: nonmonotonic velocityvs. substrate curves are often taken as evidence for two different substratebinding sites. However, a branched reaction scheme in which only one substrate binds per complete cycle can lead to a nonmonotonic response (see Segel, I.H. 1975. Enzyme Kinetics. pp. 657–659. John Wiley & Sons, New York). Some analytical constraints on the relative sizes of the rate constants of a branched reaction mechanism that give rise to nonmonotonic responses are derived. There are two necessary conditions. (i) The rate of at least one step in the branched pathway must be less than the rate of the step after the branch. (ii) The rate of the pathway in which S binds first must be slower than the rate of the other pathway. Analogous cases give rise to nonmonotonic currentvs. membrane potential curves. A branched mechanism for the Na/K pump provides an alternative explanation for a nonmonotonic pump currentvs. membrane potential relationship.

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References

  • Botts, J. 1957. Typical behavior of some simple models of enzyme action.Trans. Faraday Soc. 54,593–604

    Google Scholar 

  • DeWeer, P., Gadsby, D.C., Rakowski, R.F. 1988. Voltage dependence of the Na−K pump.Annu. Rev. Physiol. 50:225–241

    PubMed  Google Scholar 

  • Eisner, D.A., Lederer, W.J. 1985. Na−Ca exchange: Stoichiometry and electrogenicity.Am. J. Physiol. 248:C189-C202

    PubMed  Google Scholar 

  • Ferdinand, W. 1966. The interpretation of non-hyperbolic rate curves for two-substrate enzymes.Biochem. J. 98:278–283

    PubMed  Google Scholar 

  • Fröhlich, O. 1984. How channel-like is a biological carrier? Studies with the erythrocyte anion transporter.Biophys. J. 45:93–94

    Google Scholar 

  • Gadsby, D.C., Kimura, J., Noma, A. 1985. Voltage dependence of Na/K pump current in isolated heart cells.Nature (London) 315:63–65

    Google Scholar 

  • Gunn, R.B., Frohlich, O., King, P.A., Shoemaker, D.G. 1989 Anion transport.In. Red Blood Cell Membranes. P. Agre and J.C. Parker, editors. pp. 563–596. Marcel Dekker, New York

    Google Scholar 

  • Hansen, U.-P., Gradmann, D., Sanders, D., Slayman, C.L. 1981. Interpretation of current-voltage relationships for “active” ion transport systems. I. Steady-state reaction-kinetic analysis of Class-I mechanisms.J. Membrane Biol. 63:165–190

    Google Scholar 

  • Hearon, J.Z., Bernhard, S.A., Friess, S.L., Botts, D.J., Morales, M.F. 1959. Enzyme kinetics.In: The Enzymes. P.D. Boyer, H. Lardy, and K. Myrback, editors. pp. 49–142, Academic, New York

    Google Scholar 

  • Kaplan, J.H. 1985. Ion movements through the sodium pump.Annu. Rev. Physiol. 47:535–544

    PubMed  Google Scholar 

  • Karlish, S.J.D., Goldschleger, R., Shahak, Y., Rephaeli, A. 1988. Charge transfer by the Na/K pump.Prog. Clin. Biol. Res. 268A:519–524

    PubMed  Google Scholar 

  • King, E.L. 1956. Unusual kinetic consequences of certain enzyme catalysis mechanisms.J. Phys. Chem. 60:1378–1380

    Google Scholar 

  • Lafaire, A.V., Schwarz, W. 1986. Voltage dependence of the rheogenic Na+/K+ ATPase in the membrane of oocytes ofXenopus laevis.J. Membrane Biol. 91:43–51

    Google Scholar 

  • Läuger, P. 1984. Thermodynamic and kinetic properties of electrogenic ion pumps.Biochim. Biophys. Acta 779:307–341

    PubMed  Google Scholar 

  • Läuger, P. 1985. Channels with multiple conformational states: Interrelation with carriers and pumps.Curr. Top. Membr. Transp. 21:309

    Google Scholar 

  • Milanick, M.A. 1987. One voltage dependent step per pump cycle can result in a region of negative conductance (negative slope of a fluxvs. voltage curve) if the cycle is branched.Physiologist 30:224 (Abstr.)

    Google Scholar 

  • Milanick, M.A., Gunn, R.B. 1982. Proton-sulfate co-transport: Mechanism of H and sulfate addition to the chloride transporter of human red blood cells.J. Gen. Physiol. 79:87–113

    PubMed  Google Scholar 

  • Moczydlowski, E.G., Fortes, P.A.G. 1981. Inhibition of sodium and potassium adenosine triphosphatase by 2′,2′-O-(2,4,6-trinitrocyclohexadenylidine) adenine nucleotide. Implications for the structure and mechanism of the Na: K pump.J. Biol. Chem. 256:2357–2366

    PubMed  Google Scholar 

  • Rakowski, R.F., Gadsby, D.C., DeWeer, P. 1989. Stoichiometry and voltage dependence of the sodium pump in voltage-clamped internally dialyzed squid giant axon.J. Gen. Physiol. 93:903–941

    PubMed  Google Scholar 

  • Rakowski, R.F., Paxson, C.L. 1988. Voltage dependence of Na/K pump current inXenopus oocytes.J. Membrane Biol. 106:173–182

    Google Scholar 

  • Rakowski, R.F., Vasilets, L.A., Schwarz, W. 1990. Conditions for a negative slope in the current-voltage relationship of the Na/K pump inXenopus oocytes.Biophys. J. 57:182a

    Google Scholar 

  • Sachs, J.R. 1986. Potassium-potassium exchange, as part of the over-all reaction mechanism of the sodium pump of the human red blood cell.J. Physiol. (London) 374:221–244

    Google Scholar 

  • Sachs, J.R. 1988. Phosphate inhibition of the human red cell sodium pump: Simultaneous binding of adenosine tripshosphate and phosphate.J. Physiol. (London) 400:545–574

    Google Scholar 

  • Sanders, D. 1986. Generalized kinetic analysis of ion-driven cotransport systems: II. Random ligand binding as a simple explanation for non-Michaelian kinetics.J. Membrane Biol. 90:67–87

    Google Scholar 

  • Schweigert, B., Lafaire, A.V., Schwarz, W. 1988. Voltage dependence of the Na−K ATPase: Measurements of ouabain-dependent membrane current and ouabain binding in oocytes ofXenopus laevis.Pfluegers Arch. 412:579–588

    Google Scholar 

  • Segel, I.H. 1975. Enzyme Kinetics. pp. 460–461, 646–648, and 657–659. John. Wiley & Sons, New York

    Google Scholar 

  • Stein, W.D. 1986. Transport and Kinetics Across Cell Membranes. pp. 475–571. Academic, New York

    Google Scholar 

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Milanick, M.A. Branched reaction mechanism for the Na/K pump as an alternative explanation for a nonmonotonic currentvs. membrane potential response. J. Membrain Biol. 119, 33–39 (1991). https://doi.org/10.1007/BF01868538

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  • DOI: https://doi.org/10.1007/BF01868538

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