The Journal of Membrane Biology

, Volume 86, Issue 1, pp 61–67 | Cite as

Selective transport of Li+ across lipid bilayer membranes mediated by an ionophore of novel design (ETH1644)

  • Amira Zeevi
  • Rimona Margalit


The neutral noncyclic, lithium-selective ionophore ETH1644, which is structurally different from previously available ionophores of this type, is a selective carrier of Li in lipid bilayer membranes of various lipid composition. The ionophore forms a 2∶1 carrier/cation complex, and the rate-limiting step in the overall transport process is the diffusion of the carrier/ion complex across the membrane.

The selectivity sequence for lithiumvs. other ions normally found in biological systems is: Li+ (1)>Na+ (0.017)≥K+ (0.017) >Cl (0.001), Ca2+ and Mg2+ are impermeant. At neutral pH protons do not interfere with the Li+-carrying ability of this ionophore. On the basis of structural differences and supported by conductance data, it is argued that the improved selectivity of Li+ over the other alkali cations is due more to a decrease in the affinities of the ionophore for the latter cations that to an increase of its affinity to Li+. This ionophore can also act as a carrier of biogenic amines (catecholes, indoles and derivatives), with the structure of the permeant species and mechanism of permeation similar to that observed with the alkali cations. The selectivity sequence is: tryptamine (18.1)>phenylethylamine (11.6)> tyramine (2.4)>Li+(1)>serotonin (0.34)>epinephrine (0.09) >dopamine (0.05)>norepinephrine (0.02), showing the ionophore to be more selective to Li+ than to any of the neurotransmitters studies.

Key Words

lithium ionophore ion-transport lipid bilayers biogenic amines 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Andersen, O.S. 1978. Ion transport across simple lipid membranes.In: Renal Functions. G.E. Giebisch and E.F. Piercell, editors. pp. 71–99. J. Macy, Jr., Foundation, New YorkGoogle Scholar
  2. 2.
    Cotton, F.A., Wilkinson, C. 1962. Advanced Inorganic Chemistry. Interscience, New YorkGoogle Scholar
  3. 3.
    Eisenman, G. 1961. On the elementary atomic origins of equilibrium ionic specificity.In: Symposium on Membrane Transport. A. Kleinzeller and A. Kotyk, editors. pp. 163–179. Academic Press, New YorkGoogle Scholar
  4. 4.
    Eisenman, G., Ciani, S., Szabo, G. 1968. Some theoretically expected and experimentally observed properties of lipid bilayer membranes containing neutral molecular carriers of ions.Fed. Proc. 27:1289–1304PubMedGoogle Scholar
  5. 5.
    Gallicchio, V.S., Chen, M.G. 1981. Influence of lithium on proliferation of hematopoietic stem cells.Exp. Hematol. 9:804–810PubMedGoogle Scholar
  6. 6.
    Guggi, M., Fiedler, U., Prestsch, E., Simon, W. 1975. A lithium ion-selective electrode based on a neutral carrier.Anal. Lett. 8:857–866Google Scholar
  7. 7.
    Hladky, S.B., Haydon, D.A. 1973. Membrane conductance and surface potential.Biochim. Biophys. Acta 318:464–468Google Scholar
  8. 8.
    Johnson, F.N. 1975. Lithium Research and Therapy. Academic Press, LondonGoogle Scholar
  9. 9.
    Kaufman, K., Silman, I. 1973. The induction by protons of ion channels through lipid bilayer membranes.Biophys. Chem. 18:89–99Google Scholar
  10. 10.
    Krasne, S., Eisenman, G. 1976. Influence of molecular variations of ionophore and lipid on the selective ion permeability of membranes: I. Tetranactin and the methylation of nonactin-type carries.J. Membrane Biol. 30:1–44Google Scholar
  11. 11.
    Levy, R., Livne, A. 1984. The erythrocyte membrane in essential hypertension characterization of the temperature dependence of lithium efflux.Biochim. Biophys. Acta 769:41–48PubMedGoogle Scholar
  12. 12.
    Margalit, R., Azuri-Yam, R., Zeevi, A. 1984. Serotonin, dopamine and related molecules are transported selectively by noncyclic neutral Li+-selective ionophores: Implications for electrodes and for neurobiological studies.In: Recent Advances in the Theory and Application of Ion-Selective Electrodes in Physiology and Medicine. M. Kessler and D.C. Harrison, editors. Springer-Verlag (in press)Google Scholar
  13. 13.
    Margalit, R., Eisenman, G. 1979. Some binding properties of the peptide backbone inferred from studies of a neutral noncylic carrier having imide ligands.In: Peptides: Structure and Biological Functions. E. Gross and G. Meienhofer, editors. pp. 665–679. Pierce Chemical Company, Rockford, IllinoisGoogle Scholar
  14. 14.
    Margalit, R., Eisenman, G. 1981. Ionic permeation of lipid bilayer membranes mediated by a neutral noncyclic Li+-selective carrier having imide and ether ligands: I. Selectivity among monovalent cations.J. Membrane Biol. 61:209–219Google Scholar
  15. 15.
    Margalit, R., Shanzer, A. 1981. A study of Li+-selective permeation through lipid bilayer membranes mediated by a new ionophore (AS701).Biochim. Biophys. Acta 649:441–448PubMedGoogle Scholar
  16. 16.
    Margalit, R., Shanzer, A. 1982. New Li+-selective ionophores with potential ability to mediate Li+ transportin vivo: Ionic selectivity and relative potencies studied in model membranes.Pfluegers Arch. 395:87–92Google Scholar
  17. 17.
    Margalit, R., Zeevi, A., Shanzer, A. 1984. Electrogenic and selective transport of biogenic amines across lipid bilayer membranes mediated by a neutral ionophore.Biochim. Biophys. Acta 774:193–199Google Scholar
  18. 18.
    Mumtaz, M., Narasimhachari, W., Friedel, R.O., Pandy, G.N., Davis, J.M. 1982. Evaluation of fluorimetric assay methods for serotonin in platelets, plasma and whole blood samples by comparison with GC-MS-SIM techniques.Res. Comm. Chem. Pathol. Pharmacol. 36:45–60Google Scholar
  19. 19.
    Neff, N.H., Karoun, F. 1982. Quantitative gas chromatography-mass spectrometry (GC-MS) of biogenic amines: Theory and practice.In: Modern Methods in Pharmacol. Vol. 1, pp. 39–54. S. Spector and N. Back, editors. Alan R. Liss, New YorkGoogle Scholar
  20. 20.
    Reisberg, B., Gershon, S. 1979. Side-effects associated with lithium therapy.Arch. Gen. Psychiat. 36:879–887PubMedGoogle Scholar
  21. 21.
    Rosental, N.E., Goodwin, F.K. 1982. The role of the Li+ ion in medicine.Annu. Rev. Med. 33:555–568PubMedGoogle Scholar
  22. 22.
    Rossof, A.H., Robinson, W.A., editors. 1980. Lithium Effects on Granulopoiesis and Immune Function. Plenum Press, New YorkGoogle Scholar
  23. 23.
    Schou, M. 1983. Lithium. Treatment of Manic-depressive Illness. A Practical Guide. (2nd rev. ed.) Karger, Basel—New YorkGoogle Scholar
  24. 24.
    Shanzer, A., Samuel, D., Korenstein, R. 1983. Lipophylic lithium ion carriers.J. Am. Chem. Soc. 105:3815–3818Google Scholar
  25. 25.
    Stein, R.S., Howard, C.A., Brennan, M., Czorniak, M. 1981. Lithium carbonate and granulocyte production: Dose optimisation.Cancer 48:2696–2701Google Scholar
  26. 26.
    Zhukov, A.F., Erne, D., Amman, D., Guggi, M., Pretsch, E., Simon, W. 1981. Improved lithium ion-selective electrode based on a lipophylic diamide as a neutral carrier.Anal. Chim. Acta 131:117–122Google Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • Amira Zeevi
    • 1
  • Rimona Margalit
    • 1
  1. 1.Department of Biochemistry, George S. Wise Life Science CenterTel-Aviv UniversityTel-AvivIsrael

Personalised recommendations