Characterizing the Electrical Behavior of an Open Channel via the Energy Profile for Ion Permeation

A Prototype Using a Fluctuating Barrier Model for the Acetylcholine Receptor Channel
  • George Eisenman
  • John A. Dani
Part of the Series of the Centro de Estudios Científicos de Santiago book series (SCEC)


The fundamental importance of the energy profile in determining the permeability parameters (e.g., selectivity, conductance, and binding) of a channel with classical, static structure has been discussed elsewhere (Eisenman and Horn, 1983). Here we examine what happens to the current-voltage and conductance-concentration behaviors when ä more dynamic view is taken, namely, one in which significant fluctuations in the energy profile can occur on the same time scale as ion translocation. The surfaces of proteins in solution execute thermally excited motion with a root-mean-square amplitude of 1 to 2 Å (Karplus and McCammon, 1983; McCammon, 1984; McCammon and Karplus, 1983). If such motion extended into the pore, it would occur over a significant fraction of the estimated diameter of biological ionic channels and would be expected to perturb significantly the energy profile for ion permeation. Lauger et al. (1980; Lauger, 1984) were the first to extend barrier models of ionic permeation in order to allow for the possibility that the energy profile could fluctuate on the same time scale as ionic migration. They showed that when such fluctuations are coupled to ion translocation, even for a singly occupied channel, they lead to behavior usually associated with multiple occupancy, a conclusion supported by Ciani (1984).


Energy Profile Versus Data Fluctuation Rate Microscopic Reversibility Empty Channel 
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  1. Adams, P. R., 1979, A completely symmetrical barrier model for endplate channels, Biophys. J. 25:70a.Google Scholar
  2. Ciani, S., 1984, Coupling between fluxes in one-particle pores with fluctuating energy profiles, Biophys. J. 46:249–252.PubMedCrossRefGoogle Scholar
  3. Dani, J. A., and Eisenman, G., 1986, Electrical behavior of the acetylcholine receptor channel for mono- and divalent cations, J. Gen. Physiol, (submitted).Google Scholar
  4. Dani, J. A., and Eisenman, G., 1985, Acetylcholine receptor channel permeability properties for mono- and divalent cations, Biophys. J. 47:43a.CrossRefGoogle Scholar
  5. Dani, J. A., and Eisenman, G., 1986, Electrical behavior of the acetylcholine receptor chanel for mono- and divalent cations, J. Gen. Physiol. (submitted).Google Scholar
  6. Eisenman, G., 1986, Electrical signs of rapid fluctuations in the energy profile of an open channel, in Proceedings of International Symposium on Ion Transport through Membranes. Nagoya, Japan, 1985, Academic Press, Tokyo.Google Scholar
  7. Eisenman, G., and Dani, J. A., 1985, A fluctuating 2 barrier 1 site model compared with electrical data from the acetylcholine receptor channel, in Water and Ions in Biological Systems, Proceedings of the third International Conference. (A. Pullman, V. Vasilescu, and L. Packer, eds.), Union of Societies for Medical Sciences, pp 437–450. Bucharest, Romania. Google Scholar
  8. Eisenman, G., and Horn, R., 1983, Ionic selectivity revisited: The role of kinetic and equilibrium processes in ion permeation through channels, J. Membr. Biol. 76:197–225.PubMedCrossRefGoogle Scholar
  9. Eisenman, G., and Sandblom, J., 1983, Energy barriers in ionic channels: Data for gramicidin A interpreted using a single-file (3B4S) model having 3 barriers separating 4 sites, in Physical Chemistry of Transmembrane Ion Motions (G. Spach, ed.), Elsevier, Amsterdam, pp. 329–348.Google Scholar
  10. Eisenman, G., Sandblom, J., and Neher, E., 1978, Interactions in cation permeation through the gramicidin channel Cs, Rb, K, Na, Li, Tl, H, and effects of anion binding, Biophys. J. 22:307–340.PubMedCrossRefGoogle Scholar
  11. Eisenman, G., Dani, J. A., and Sandblom, J., 1985, Recent studies on the energy profiles underlying permeation and ion selectivity of the gramicidin and acetylcholine receptor channels, in: Ion Measurement in Physiology and Medicine (M. Kessler, D. K. Harrison, and J. Hoper, eds.), pp. 54–66, Springer-Verlag, New York.CrossRefGoogle Scholar
  12. Eyring, H., Lumry, R., and Woodbury, J. W., 1949, Rec. Chem. Prog. 10:100–114.Google Scholar
  13. Guy, H. R., 1984, A structural model of the acetylcholine receptor channel based on partition energy and helix packing calculations, Biophys. J. 45:249–261.PubMedCrossRefGoogle Scholar
  14. Hagglund, J. V., Eisenman, G., and Sandblom, J. P., 1984, Single-salt behavior of a symmetrical 4-site channel with barriers at its middle and ends, Bull. Math. Biol. 46:41–80.Google Scholar
  15. Hamilton, W. C., 1964, Statistics in Physical Science, Ronald Press, New York.Google Scholar
  16. Hille, B., and Schwarz, W., 1978, Potassium channels as multi-ion single-file pores, J. Gen. Physiol. 72:409–442.PubMedCrossRefGoogle Scholar
  17. Horn, R., and Brodwick, M., 1980, Acetylcholine-induced current in perfused rat myoballs, J. Gen. Physiol. 75:297–321.PubMedCrossRefGoogle Scholar
  18. Karplus, M., and McCammon, J. A., 1983, Dynamics of proteins: Elements and function, Annu. Rev. Biochem. 53:263–300.CrossRefGoogle Scholar
  19. Lauger, P., 1973, Ion transport through pores: A rate-theory analysis, Biochim. Biophys. Acta 311:423–441.PubMedCrossRefGoogle Scholar
  20. Lauger, P., 1984, Channels with multiple conformational states: Interrelations with carriers and pumps, Curr. Top. Membr. Transport 21:309–326.Google Scholar
  21. Lauger, P., Stephan, W., and Frehland, E., 1980, Fluctuations of barrier structure in ionic channels, Biochim. Biophys. Acta 602:167–180.PubMedCrossRefGoogle Scholar
  22. Lewis, C. A., and Stevens, C. F., 1979, Mechanism of ion permeation through channels in a postsynaptic membrane, in Membrane Transport Processes, Vol. 3 (C. F. Stevens and R. W. Tsien, eds.), Raven Press, New York, pp. 133–151.Google Scholar
  23. Marchais, D., and Marty, A., 1979, Interaction of permeant ions with channels activated by acetylcholine in Aplysia neurones, J. Physiol. (Lond.) 297:9–45.Google Scholar
  24. McCammon, J. A., 1984, Protein dynamics, Rep. Prog. Phys. 47:1–46.CrossRefGoogle Scholar
  25. McCammon, J. A., and Karplus, M., 1983, The dynamic picture of protein structure, Acc. Chem. Res. 16:187–193.CrossRefGoogle Scholar
  26. Powell, M. J. D., 1977, A fast algorithm for nonlinearity constrained optimization calculations, in: Numerical Analysis, Lecture Notes in Mathematics No. 630, Dundee 1977 (G. A. Watson, ed.), Springer-Verlag, Berlin.Google Scholar
  27. Record, M. T., Jr., Anderson, C. F., and Lohman, T. M., 1978, Thermodynamic analysis of ion effects on the binding and conformational equilibria of proteins and nucleic acids: The roles of ion association or release, screening, and ion effects on water activity, Q. Rev. Biophys. 11:103–178.PubMedCrossRefGoogle Scholar
  28. Sandblom, J., Eisenman, G., and Hagglund, J., 1983, Multioccupancy models for single filing ionic channels: Theoretical behavior of a four-site channel with three barriers separating the sites, J. Membr. Biol. 71:61–78.PubMedCrossRefGoogle Scholar
  29. Sigworth, F. J., 1982, Fluctuations in the current through open ACh-receptor channels, Biophys. J. 37:309a.Google Scholar
  30. Sigworth, F. J., 1985, Open channel noise. I. Noise in acetylcholine receptor currents suggests conformational fluctuations, Biophys. J. 47:709–720.PubMedCrossRefGoogle Scholar
  31. Unwin, P. N. T., and Zamphighi, G., 1980, Structure of the junction between communicating cells, Nature 283:545–549.PubMedCrossRefGoogle Scholar
  32. Urban, B. W., Hladky, S. B., and Haydon, D. A., 1980, Ion movements in gramicidin pores. An example of single-file transport, Biochim. Biophys. Acta 602:331–354.PubMedCrossRefGoogle Scholar
  33. Von Hippel, P. H., and Schleich, T., 1969, The effects of neutral salts on the structure and conformational stability of macromolecules in solution, in Biological Macromolecules. Vol. 2: Structure and Stability of Biological Macromolecules (S. N. Timasheff and G. Fasman, eds.), Marcel Dekker, New York, pp. 417–574.Google Scholar
  34. Yellen, G., 1984, Ionic permeation and blockade in Ca2+-activated K+ channels of bovine chromaffin cells, J. Gen. Physiol. 84:157–186.PubMedCrossRefGoogle Scholar
  35. Young, E. F., Ralston, E., Blake, J., Ramachandran, J., Hall, Z. W., and Stroud, R. M., 1985, Topological mapping of acetylcholine receptor: Evidence for a model with five transmembrane segments and a cytoplasmic COOH-terminal peptide, Proc. Natl. Acad. Sci. U.S.A. 82:626–630.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • George Eisenman
    • 1
  • John A. Dani
    • 1
  1. 1.Department of Physiology, Medical SchoolUniversity of CaliforniaLos AngelesUSA

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