Ion-Coupled Transport across Biological Membranes

  • Stanley G. Schultz


Only a rudimentary understanding of the principles of classical thermodynamics is needed to appreciate that the flow of an uncharged substance from a region of lower concentration to a region of higher concentration or the flow of a charged substance from a region of lower electrochemical potential to a region of higher electrochemical potential cannot take place unless the processes responsible for these flows are linked or coupled to a supply of energy. Such flows, loosely referred to as “active” or “uphill,” are commonplace in biological systems and the thrust of many investigations is to identify the immediately responsible source(s) of energy.


Amino Acid Transport Renal Proximal Tubule Ehrlich Ascites Tumor Cell Electrical Potential Difference Couple Solute 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Katchalsky, A., and P. F. Curran. 1965. Nonequilibrium Thermodynamics in Biophysics. Harvard Univ. Press, Cambridge, Massachusetts.Google Scholar
  2. 2.
    Kedem, O. 1961. Criteria of active transport. In: Membrane Transport and Metabolism. A. Kleinzeller and A. Kotyk, eds. Czech. Acad. Sci., Prague. pp. 87 - 93.Google Scholar
  3. 3.
    Rosenberg, T. 1948. On accumulation and active transport in biological systems. I. Thermodynamic considerations. Acta Chem. Scand. 2: 14 - 33.CrossRefGoogle Scholar
  4. 4.
    Curran, P. F., and S. G. Schultz. 1968. Transport across membranes: General principles. In: Handbook of Psysiology, Section 6, The Alimentary Canal, Vol. III: Intestinal Absorption. C. F. Code, ed. Am. Physiol. Soc., Washington, D.C. Chap. 65, pp. 1217 - 1243.Google Scholar
  5. 5.
    Schultz, S. G. 1968. Mechanisms of absorption. In: Biological Membranes. R. M. Dowben, ed. Little, Brown, Boston. pp. 59 - 108.Google Scholar
  6. 6.
    Mitchell, P. 1970. Reversible coupling between transport and chemical reactions. In: Membranes and Ion Transport, Vol. 1. E. E. Bittar, ed. Wiley (Interscience), New York. pp. 192 - 256.Google Scholar
  7. 7.
    Wilbrandt, W., and T. Rosenberg. 1965. The concept of carrier transport and its corollaries in pharmacology. Pharmacol. Rev. 13: 109 - 183.Google Scholar
  8. 8.
    Schultz, S. G., and P. F. Curran. 1970. Coupled transport of sodium and organic solutes. Physiol. Rev. 50: 637 - 718.PubMedGoogle Scholar
  9. 9.
    Kimmich, G. A. 1973. Coupling between Na and sugar transport in small intestine. Biochim. Biophys. Acta 300: 31 - 78.PubMedCrossRefGoogle Scholar
  10. 10.
    Christensen, H. N., C. DeCespedes, M. E. Handlog-ten, and G. Ronquist. 1973. Energization of amino acid transport, studied for the Ehrlich ascites tumor cell. Biochim. Biophys. Acta 300: 487 - 522.PubMedCrossRefGoogle Scholar
  11. 11.
    Harold, F. M. 1972. Conservation and transformation of energy by bacterial membranes. Bacteriol. Rev. 36: 172 - 230.PubMedGoogle Scholar
  12. 12.
    Boos, W. 1974. Bacterial transport. Annu. Rev. Biochem. 43: 123 - 146.PubMedCrossRefGoogle Scholar
  13. 13.
    Slayman, C. L. 1974. Proton pumping and generalized energetics of transport: A review. In: Membrane Transport in Plants. E. Zimmerman and J. Dainty, eds. Springer-Verlag, Berlin/New York. pp. 107 - 119.CrossRefGoogle Scholar
  14. 14.
    Heinz, E. 1972. Na-Linked Transport of Organic Solutes. Springer-Verlag, Berlin/New York.CrossRefGoogle Scholar
  15. 15.
    Eddy, A. A. 1968. A net gain of sodium ions and a net loss of potassium ions accompanying the uptake of glycine by mouse ascites tumor cells in the presence of sodium cyanide. Biochem. J. 108: 195 - 206.PubMedGoogle Scholar
  16. 16.
    Schafer, J. A., and J. A. Jacquez. 1967. Change in Na uptake during amino acid transport. Biochim. Biophys. Acta 135: 1081 - 1083.PubMedCrossRefGoogle Scholar
  17. 17.
    Vidaver, G. A. 1964. Some tests of the hypothesis that the sodium ion gradient furnishes the energy for glycine active transport by pigeon red cells. Biochemistry 3: 803 - 808.PubMedCrossRefGoogle Scholar
  18. 18.
    Curran, P. F., S. G. Schultz, R. A. Chez, and R. E. Fuisz. 1967. Kinetic relations of the Na-amino acid interaction at the mucosal border of intestine. J. Gen. Physiol. 50: 1261 - 1286.PubMedCrossRefGoogle Scholar
  19. 19.
    Peterson, S. C., A. M. Goldner, and P. F. Curran. 1970. Glycine transport in rabbit ileum. Am. J. Physiol. 219: 1027 - 1032.PubMedGoogle Scholar
  20. 20.
    Frizzell, R. A., H. N. Nellans, and S. G. Schultz. 1973. Effects of sugars and amino acids on sodium and potassium influx in rabbit ileum. J. Clin. Invest. 52: 215 - 217.PubMedCrossRefGoogle Scholar
  21. 21.
    Rose, R. C., and S. G. Schultz. 1971. Studies on the electrical potential profile across rabbit ileum: Effects of sugars and amino acids on transmural and transmucosal electrical potential differences. J. Gen. Physiol. 57: 639 - 663.PubMedCrossRefGoogle Scholar
  22. 22.
    White, J. F., and W. McD. Armstrong. 1971. Effect of transported solutes on membrane potentials in bullfrog small intestine. Am. J. Physiol. 221: 194 - 201.PubMedGoogle Scholar
  23. 23.
    Samarzija, I., and E. Fromter. 1975. Electrical studies on amino acid transport across brush border membrane of rat proximal tubule in vivo. Pfluegers Arch. 359: R119.Google Scholar
  24. 24.
    Goldner, A. M., S. G. Schultz, and P. F. Curran. 1969. Sodium and sugar fluxes across the mucosal border of rabbit ileum. J. Gen. Physiol. 53: 362 - 283.PubMedCrossRefGoogle Scholar
  25. 25.
    Maruyama, T., and T. Hoshi. 1972. The effect of D-glucose on the electrical potential profile across the proximal tubule of Newt kidney. Biochim. Biophys. Acta 282: 214 - 225.PubMedCrossRefGoogle Scholar
  26. 26.
    Fromter, E., and K. Luer. 1973. Electrical studies on sugar transport kinetics of rat proximal tubule. Pfluegers Arch. 343: R47.Google Scholar
  27. 27.
    Berger, E., E. Long, and G. Semenza. 1972. The sodium activation of biotin absorption in hamster small intestine in vitro. Biochim. Biophys. Acta 255: 873 - 887.CrossRefGoogle Scholar
  28. 28.
    Holt, P. R. 1964. Intestinal absorption of bile salts in the rat. Am. J. Physiol. 207: 1 - 7.PubMedGoogle Scholar
  29. 29.
    Matthews, D. M. 1975. Intestinal transport of peptides. In: Intestinal Absorption and Malabsorption. T. Z. Csaky, ed. Raven Press, New York. pp. 95 - 111.Google Scholar
  30. 30.
    Rubino, A., M. Field, and H. Shwachman. 1971. Intestinal transport of amino acid residues of dipeptides. I. Influx of the glycine residue of glycyl-L-proline across mucosal border. J. Biol. Chem. 246: 3542 - 3548.PubMedGoogle Scholar
  31. 31.
    Berndt, W. O., and E. C. Beechwood. 1965. Influence of inorganic electrolytes and ouabain on uric acid transport. Am. J. Physiol. 208: 642 - 648.PubMedGoogle Scholar
  32. 32.
    Quastel, J. H. 1965. Molecular transport at cell membranes. Proc. R. Soc. Lond. 163B: 169 - 196.PubMedCrossRefGoogle Scholar
  33. 33.
    Schultz, S. G., R. A. Frizzell, and H. N. Nellans. 1974. Ion transport by mammalian small intestine. Annu. Rev. Physiol. 36: 51 - 91.PubMedCrossRefGoogle Scholar
  34. 34.
    Nellans, H. N., R. A. Frizzell, and S. G. Schultz. 1973. Coupled sodium-chloride influx across the brush border of rabbit ileum. Am. J. Physiol. 225: 467 - 475.PubMedGoogle Scholar
  35. 35.
    Frizzell, R. A., M. Dugas, and S. G. Schultz. 1975. Sodium chloride transport by rabbit gallbladder: Direct evidence for a coupled NaC1 influx process. J. Gen. Physiol. 65: 769 - 795.PubMedCrossRefGoogle Scholar
  36. 36.
    Nellans, H. N., R. A. Frizzell, and S. G. Schultz. 1974. Brush border processes and transepithelial Na and Cl transport by rabbit ileum. Am. J. Physiol. 226: 11311141.Google Scholar
  37. 37.
    Blaustein, M. P. 1974. The interrelationship between sodium and calcium fluxes across cell membranes. Rev. Physiol. Biochem. Pharmacol. 70: 33 - 82.PubMedCrossRefGoogle Scholar
  38. 38.
    Alexander, W. D., and J. Wolff. 1964. Cation requirements for iodide transport. Arch. Biochem. Biophys. 106: 525 - 526.PubMedCrossRefGoogle Scholar
  39. 39.
    Siegenthaler, P. A., M. M. Belsky, and S. Goldstein. 1967. Phosphate uptake in an obligately marine fungus: A specific requirement for sodium. Science 155: 93 - 94.PubMedCrossRefGoogle Scholar
  40. 40.
    West, I. C., and P. Mitchell. 1973. Stoichiometry of lactose-H symport across the plasma membrane of Escherichia coli. Biochem. J. 132: 587 - 592.Google Scholar
  41. 41.
    Kashket, E. R., and T. H. Wilson. 1973. Proton-coupled accumulation of galactoside in Streptococcus lactis 7962. Proc. Natl. Acad. Sci. U.S.A. 70: 2866 - 2869.PubMedCrossRefGoogle Scholar
  42. 42.
    Asghar, S. S., E. Levin, and F. M. Harold. 1973. Accumulation of neutral amino acids by Streptococcus faecalis. Energy coupling by a proton-motive force. J. Biol. Chem. 248: 5225 - 5233.PubMedGoogle Scholar
  43. 43.
    Seaston, A., C. Inkson, and A. A. Eddy. 1973. The absorption of protons with specific amino acids and carbohydrates by yeast. Biochem. J. 134: 1031 - 1043.PubMedGoogle Scholar
  44. 44.
    Eddy, A. A., and J. A. Nowacki. 1971. Stoichiometrical proton and potassium movements accompanying the absorption of amino acids by the yeast Saccharomyces carlsbergensis. Biochem. J. 122: 701 - 711.Google Scholar
  45. 45.
    Slayman, C. L., and C. W. Slayman. 1974. Depolarization of the plasma membrane of Neurospora during active transport of glucose: Evidence for a proton-dependent co-transport system. Proc. Natl. Acad. Sci. U.S.A. 71 :1935-1939.Google Scholar
  46. 46.
    Komor, E., and W. Tanner. 1974. The hexose-proton cotransport system of Chlorella. J. Gen. Physiol. 64: 568 - 581.CrossRefGoogle Scholar
  47. 47.
    Harold, F. M., and J. R. Baarda. 1968 Inhibition of membrane transport in Streptococcus faecalis by un-couplers of oxidate phosphorylation and its relationship to proton conduction. J. Bacteriol. 96: 2025 - 2034.PubMedGoogle Scholar
  48. 48.
    Riggs, T. R., L. M. Walker, and H. N. Christensen. 1958. Potassium migration and amino acid transport. J. Biol. Chem. 233: 1479 - 1484.PubMedGoogle Scholar
  49. 49.
    Crane, R. K. 1965. Na-dependent transport in the intestine and other animal tissues. Fed. Proc. 24: 1000 - 1005.PubMedGoogle Scholar
  50. 50.
    Eddy, A. A. 1968. The effects of varying the cellular and extracellular concentrations of sodium and potassium ions on the uptake of glycine by mouse ascites tumour cells in the presence and absence of sodium cyanide. Biochem. J. 108: 489 - 498.PubMedGoogle Scholar
  51. 51.
    Hajjar, J. J., A. S. Lamont, and P. E. Curran. 1970. The sodium-alanine interaction in rabbit ileum: Effect of sodium on alanine fluxes. J. Gen. Physiol. 55: 277296.Google Scholar
  52. 52.
    Murer, H., and U. Hopfer. 1973. Interaction between sugar and amino acid transport in the small intestine. In: Biochemical and Clinical Aspects of Peptide and Amino Acid Absorption. K. Rommel and H. Goebell, eds. Schattauer Verlag, Stuttgart. pp. 61 - 65.Google Scholar
  53. 53.
    Murer, H., U. Hopfer, E. Kinne-Saffran, and R. Kinne. 1974. Glucose transport in isolated brush-border and lateral basal plasma membrane vesicles from intestinal epithelial cells. Biochim. Biophys. Acta 345: 170 - 179.PubMedCrossRefGoogle Scholar
  54. 54.
    Sigrist-Nelson, K., H. Murer, and U. Hopfer. 1975. Active alanine transport in isolated brush border membranes. J. Biol. Chem. 250: 5674 - 5680.PubMedGoogle Scholar
  55. 55.
    Kinne, R., H. Murer, E. Kinne-Saffran, M. Thees, and G. Sachs. 1975. Sugar transport by renal plasma membrane vesicles. J. Membr. Biol. 21: 375 - 395.PubMedCrossRefGoogle Scholar
  56. 56.
    Aronson, P. S., and B. Sacktor. 1975. The Na gradient dependent transport of D-glucose in renal brush border membranes. J. Biol. Chem. 250: 6032 - 6039.PubMedGoogle Scholar
  57. 57.
    Colombini, M., and R. M. Johnstone. 1974. Na-gradient-stimulated AIB transport in membrane vesicles from Ehrlich ascites cells. J. Membr. Biol. 18: 315 - 334.PubMedCrossRefGoogle Scholar
  58. 58.
    Eddy, A. A. 1969. A sodium ion concentration gradient formed during the absorption of glycine by mouse ascites tumour cells. Biochem. J. 115: 505 - 509.PubMedGoogle Scholar
  59. 59.
    Curran, P. F., J. J. Hajjar, and I. M. Glynn. 1970. The sodium-alanine interaction in rabbit ileum: Effect of alanine on sodium fluxes. J. Gen. Physiol. 55: 297 - 308.PubMedCrossRefGoogle Scholar
  60. 60.
    Potaschner, S. J., and R. M. Johnstone. 1971. Cation gradients, ATP and amino acid accumulation in Ehrlich ascites cells. Biochim. Biophys. Acta 233: 91 - 103.CrossRefGoogle Scholar
  61. 61.
    Johnstone, R. M. 1972. Transport of amino acids in Ehrlich cells and mouse pancreas. In: Na-Linked Transport of Organic Solutes. E. Heinz, ed. Springer-Verlag, Berlin. pp. 51 - 67. 73.Google Scholar
  62. 62.
    Schafer, J. A., and E. Heinz. 1971. The effect of reversal of Na and K electrochemical gradients on the active transport of amino acids in Ehrlich ascites tumor cells. Biochim. Biophys. Acta 249: 15 - 33.PubMedCrossRefGoogle Scholar
  63. 63.
    A. Schafer. 1969. Na and K electrochemical potential gradients and the transport of a-aminoisobutyric acid in Ehrlich ascites tumor cells. Biochim. Biophys. Acta 193: 368 - 383.PubMedCrossRefGoogle Scholar
  64. 64.
    Ronquist, G., and H. N. Christensen. 1973. Amino acid stimulation of alkali-metal-independent ATP cleavage by an Ehrlich cell membrane preparation. Biochim Google Scholar
  65. 65.
    Forte, J. G., T. M. Forte, and E. Heinz. 1973. Isolation of plasma membranes from Ehrlich ascites tumor cells. 77. Influence of amino acids on (Na+K)-ATPase and K-stimulated phosphatase. Biochim. Biophys. Acta 298: 827 - 841.PubMedCrossRefGoogle Scholar
  66. 66.
    Geck, P., E. Heinz, and B. Pfeiffer. 1974. Evidence 78. against direct coupling between amino acid transport and ATP hydrolysis. Biochim. Biophys. Acta 339: 419425. 79.Google Scholar
  67. 67.
    Lev, A. A., and W. McD. Armstrong. 1975. Ionic activities in cells. In: Current Topics in Membranes 80. and Transport, Vol. 6. F. Bronner and A. Kleinzeller, Academic Press, New York. pp. 59 - 123. 81.Google Scholar
  68. 68.
    Itoh, S., and I. L. Schwartz. 1957. Sodium and potassium distribution in isolated thymus nucleii. Am. J. Physiol. 188: 490 - 498.PubMedGoogle Scholar
  69. 69.
    Pietrzyk, C., and E. Heinz. 1974. The sequestration of 82. Na, K and Cl in the cellular nucleus and its energetic consequences for the gradient hypothesis of amino acid transport in Ehrlich cells. Biochim. Biophys. Acta 352: 397 - 411. 83.Google Scholar
  70. 70.
    Murer, H., and U. Hopfer. 1974. Demonstration of electrogenic Na-dependent D-glucose transport in intestinal brush border membranes. Proc. Natl. Acad. 84. Sci. U.S.A. 71: 484 - 488.CrossRefGoogle Scholar
  71. 71.
    Beck, J. 1975. Electrogenic Na-dependent D-glucose transport by isolated renal cortex brush border membranes. Fed. Proc. 34: 286. 85.Google Scholar
  72. 72.
    Gibb, L. E., and A. A. Eddy. 1972. An electrogenic sodium pump as a possible factor leading to the concentration of amino acids by mouse ascites-tumour cells with reversed sodium ion concentration gradients. Biochem J. 129: 979 - 981.PubMedGoogle Scholar
  73. 73.
    Reid, M., L. E. Gibb, and A. A. Eddy. 1974. Ionophore-mediated coupling between ion fluxes and amino acid absorption in mouse ascites-tumor cells. Biochem. J. 140: 383 - 393.PubMedGoogle Scholar
  74. 74.
    Morville, M., M. Reid, and A. A. Eddy. 1973 Amino acid absorption by mouse ascites-tumour cells depleted of both endogenous amino acids and adenosine triphosphate. Biochem. J. 134: 11 - 26.PubMedGoogle Scholar
  75. 75.
    Philo, R. D., and A. A. Eddy. 1975. The electrogenicity of amino acid absorption in mouse ascites-tumour cells. Biochem. Soc. Trans. 3: 904 - 906.Google Scholar
  76. 76.
    DeCespedes, C., and H. N. Christensen. 1974. Complexity in valinomycin effects on amino acid transport. Biochim. Biophys. Acta 339: 139 - 145.PubMedCrossRefGoogle Scholar
  77. 77.
    Smith, T. C., and C. Levinson. 1975. Direct measurement of the membrane potential of Ehrlich ascites tumor cells: Lack of an effect on valinomycin and ouabain. J. Membr. Biol. 23: 349 - 365.PubMedCrossRefGoogle Scholar
  78. 78.
    Lassen, U. V., A. -M. T. Nielsen, L. Pape, and L. O. Simonsen. 1971. The membrane potential of Ehrlich ascites tumor cells. J. Membr. Biol. 6: 269 - 288.CrossRefGoogle Scholar
  79. 79.
    Glynn, I. M., and S. J. D. Karlish. 1975. The sodium pump. Annu. Rev. Physiol. 37: 13 - 55.PubMedCrossRefGoogle Scholar
  80. 80.
    Thomas, R. C. 1972. Electrogenic sodium pump in nerve and muscle cells. Physiol. Rev. 52: 563 - 594.PubMedGoogle Scholar
  81. 81.
    Jacquez, J. A., and S. G. Schultz. 1974. A general relation between membrane potential, ion activities and pump fluxes for symmetric cells in a steady state. Math. Biosci. 20: 19 - 25.CrossRefGoogle Scholar
  82. 82.
    Reid, M., and A. A. Eddy. 1971. Apparent metabolic regulation of the coupling between the potassium ion gradient and methionine transport in mouse ascites-tumor cells. Biochem. J. 124: 951 - 952.PubMedGoogle Scholar
  83. 83.
    Heinz, E., P. Geck, and C. Pietrzyk. 1975. Driving forces of amino acid transport in animal cells. Ann. N.Y. Acad. Sci. 264: 428 - 441.PubMedCrossRefGoogle Scholar
  84. 84.
    Armstrong, W. McD., B. J. Byrd, and P. M. Hamang. 1973. Energetic adequacy of Na gradients for sugar accumulation in epithelial cells of small intestine. Biochim. Biophys. Acta 330: 237 - 241.PubMedCrossRefGoogle Scholar
  85. 85.
    Heinz, E., and P. Geck. 1974. The efficiency of energetic coupling between Na flow and amino acid transport in Ehrlich cells-A revised assessment. Biochim. Biophys. Acta 339: 426 - 431.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1980

Authors and Affiliations

  • Stanley G. Schultz
    • 1
  1. 1.Department of PhysiologyUniversity of Pittsburgh, School of MedicinePittsburghUSA

Personalised recommendations