Summary
The conductance of the gramicidin channel in the presence of alkali ions is strongly reduced when divalent cations such as Ca++ or Ba++ are added to the aqueous solutions in concentrations between 0.1 and 1m. Under the same conditions, carrier-mediated alkali ion transport is not affected by Ca++ and Ba++. Different divalent cations, differ considerably in their blocking action on the gramicidin channel; the effect of Mg++ or Zn++ is much smaller than that of Ca++ and Ba++. Besides reducing the single-channel conductance, the blocking ions also change the current-voltage characteristic of the channel from a nearly, linear to a strongly saturating behavior. These observations suggest that Ca++ or Ba++ (which are not permeable themselves) bind to a site at or near the channel mouth, thereby reducing the rate by which permeable ions enter and leave the channel. The blocking effect is analyzed in terms of the potential energy profile of the permeable ion in the channel. The saturating current-voltage characteristic may be explained by the assumption that in the presence of the blocking ion the passage over the entrance barrier is rate-limiting and, at the same time, only weakly voltage-dependent.
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References
Andersen, O.S. 1975. Ion specificity of gramicidin channels. P. 369. Abstr. 5th Int. Biophys. Congress, Cogenhagen
Bamberg, E., Alpes, H., Apell, H.-J., Benz, R., Janko, K., Kolb, H.-A., Läuger, P., Gross, E. 1977. Studies on the Gramicidin Channel.In: FEBS Symposium on Biochemistry of Membrane Transport. G. Semenza and E. Carafoli, editors. Springer, Heidelberg
Bamberg, E., Benz, R. 1976. Voltage-induced thickness changes of lipid bilayer membranes and the effect of an electric field on gramicidin A channel formation.Biochim. Biophys. Acta 426:570
Bamberg, E., Läuger, P. 1973. Channel formation kinetics of gramicidin A in lipid bilayer membranesJ. Membrane Biol. 11:177
Bamberg, E., Läuger, P. 1974. Temperature-dependent properties of gramicidin A channels.Biochim. Biophys. Acta 367:127
Bamberg, E., Noda, K., Gross, E., Läuger, P. 1976. Single-channel parameters of gramicidins A, B and C.Biochim. Biophys. Acta 419:223
Benz, R., Stark, G., Janko, K., Läuger, P. 1973. Valinomycin-mediated ion transport through neutral lipid membranes: Influence of hydrocarbon chain length and temperature.J. Membrane Biol. 14:339
Bezanilla, F., Armstrong, C.M. 1972. Negative conductance caused by entry of sodium and cesium ions into the potassium channels of squid axons.J. Gen. Physiol. 60:588
Cahalan, M., Begenisich, T. 1976. Sodium channel selectivity: Dependence on internal permeant ion concentration.J. Gen. Physiol. 68:111
Chizmadjev, Y.A., Khodorov, B.J., Aityan, S.K. 1974. Analysis of the independence principle for the sodium channels of biological membranes.Bioelectrochem. Bioenergetics 1:301
Eigen, M., Maass, G. 1966. Über die Kinetik der Metallkomplexbildung der Alkali- und Erdalkaliionen in wäßrigen Lösungen.Z. Physik. Chem. N.F. 49:163
Eisenman, G., Krasne, S., Ciani, S. 1974. Further studies on ion selectivity.In: Proceedings of the International Workshop on Ion-Selective Electrodes and Enzyme Electrodes in Biology and Medicine. M. Kessler, L. Clark, D. Lübbers, I. Silver and W. Simon, editors. Urban and Schwarzenberg, München (in press)
Eisenman, G., Sandblom, J., Neher, E. 1976. Ionic selectivity, saturation, binding, and block in the gramicidin A channel: A preliminary report.In: 9th Jerusalem Symposium on Metal-Ligand Interactions in Organic and Biochemistry. B. Pullman, editor (in press)
Frankenhaeuser, B., Hodgkin, A.L. 1957. The action of calcium on the electrical properties of squid axons.J. Physiol. (London) 137:218
Frehland, E., Läuger, P. 1974. Ion transport through pores: Transient phenomena.J. Theor. Biol. 47:189
Glickson, J.D., Mayers, D.F., Settine, J.M., Urry, D.W. 1972. Spectroscopic studies on the conformation of gramicidin A. Proton magnetic resonance assignments, coupling constants, and H-D exchange.Biochemistry 11:477
Haydon, D.A., Hladky, S.B. 1972. Ion transport across thin lipid membranes: A critical discussion of mechanisms in selected systems.Q. Rev. Biophys. 5:187
Heckmann, K. 1972. Single-file diffusion.In: Biomembranes, Vol. 3, Passive Permeability of cell Membranes. pp. 127–153. F. Kreuzer and J.F.G. Slegers, editors. Plenum Press, New York
Heckmann, K., Lindemann, B., Schnakenberg, J. 1972. Current-voltage curves of porous membranes in the presence of pore-blocking ions. I. Narrow pores containing no more than one moving ion.Biophys. J. 12:683
Hille, B. 1972. The permeability of the sodium channel to metal cations in myelinated nerve.J. Gen. Physiol. 59:637
Hille, B. 1975a. Ion selectivity, saturation and block in sodium channels. A four barrier model.J. Gen. Physiol. 66:535
Hille, B. 1975b. Ionic selectivity of Na and K channels of nerve membranes.In: Membranes. A Series of Advances. G. Eisenman, editor. pp. 255–323. M. Dekker, New York
Hladky, S.B., Haydon, D.A. 1972. Ion transfer across lipid membranes in the presence of gramicidin A. I. Studies, of the unit conductance channel.Biochim. Biophys. Acta 274:294
Läuger, P. 1973. Ion transport through pores: A rate-theory analysis.Biochim. Biophys. Acta 311:423
Läuger, P., Lesslauer, W., Marti, E., Richter, J. 1967. Electrical properties of bimolecular phospholipid membranes.Biochim. Biophys. Acta 135:20
Läuger, P., Neumcke, B. 1973. Theoretical analysis of ion conductance in lipid bilayer membranes.In: Membranes. A Series of Advances. G. Eisenman, editor, Vol. 2, pp. 1–59. M. Dekker, New York
Lindemann, B. 1968. Sodium-and calcium dependence of threshold potential in frog skin excitation.Biochim. Biophys. Acta 163:424
McLaughlin, S.G.A., Szabo, G., Eisenman, G. 1971. Divalent ions and the surface potential of charged phospholipid membranes.J. Gen. Physiol. 58:667
Mueller, P., Rudin, D.O. 1967. Development of K+−Na+ discrimination in experimental bimolecular lipid membranes by macrocyclic antibiotics.Biochem. Biophys. Res. Commun. 26:398
Myers, V.B., Haydon, D.A. 1972. Ion transfer across lipid membranes in the presence of gramicidin A. II. The ion selectivity.Biochim. Biophys. Acta 274:313
Neher, E. 1975. Ionic specificity of the gramicidin channel and the thallous ion.Biochim. Biophys. Acta 401:540
Neumcke, B., Läuger, P. 1969. Nonlinear electrical effects in lipid bilayer membranes. II. Integration of the generalized Nernst-Planck equations.Biophys. J. 9:1160
Rose, B., Loewenstein, W.R. 1976. Permeability of a cell junction and the local cytoplasmic free ionized calcium concentration: A study with aequorin.J. Membrane Biol. 28:87
Sandblom, J., Eisenman, G., Neher, E. 1976. Ionic selectivity, saturation and block in gramicidin A channels. I. Theory for the electrical properties of ion selective channels having two pairs of binding sites and multiple conductance states.J. Membrane Biol. 31:383
Urry, D.A. 1971. The gramicidin A transmembrane channel: A proposed πL,D helix.Proc. Nat. Acad. Sci. USA. 68:672
Urry, D.W. 1973. Polypeptide conformation and biological function. β-Helices (πL,D-helices) as permselective transmembrane channels.In: Conformation of Biological Molecules and Polymers. E.D. Bergmann and B. Pullman, editors. The Israel Academy of Sciences and Humanities, Jerusalem
Veatch, W.R., Fossel, E.T., Blout, E.R. 1974. The conformation of gramicidin A.Biochemistry 13:5249
Woodbury, J.W. 1971. Eyring rate theory model of the current-voltage relationships of ion channels in excitable membranes.In: Chemical Dynamics: Papers in Honor of Henry Eyring, J.O. Hirschfelder and D. Henderson, editors. Advances in Chemical Physics, Vol. 21, pp. 601–617. Wiley, New York
Woodhull, A.M. 1973. Ionic blockage of sodium channels in nerve.J. Gen. Physiol. 61:687
Zwolinski, B.J., Eyring, H., Reese, C.E. 1949. Diffusion and membrane permeability.J. Phys. Chem. 53:1426
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Bamberg, E., Läuger, P. Blocking of the gramicidin channel by divalent cations. J. Membrain Biol. 35, 351–375 (1977). https://doi.org/10.1007/BF01869959
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DOI: https://doi.org/10.1007/BF01869959