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. 1970 Jul 1;56(1):100–124. doi: 10.1085/jgp.56.1.100

The Ion Permeability Induced in Thin Lipid Membranes by the Polyene Antibiotics Nystatin and Amphotericin B

Albert Cass 1, Alan Finkelstein 1, Vivian Krespi 1
PMCID: PMC2225864  PMID: 5514157

Abstract

Characteristics of nystatin and amphotericin B action on thin (<100 A) lipid membranes are: (a) micromolar amounts increase membrane conductance from 10-8 to over 10-2 Ω-1 cm-2; (b) such membranes are (non-ideally) anion selective and discriminate among anions on the basis of size; (c) membrane sterol is required for action; (d) antibiotic presence on both sides of membrane strongly favors action; (e) conductance is proportional to a large power of antibiotic concentration; (f) conductance decreases ∼104 times for a 10°C temperature rise; (g) kinetics of antibiotic action are also very temperature sensitive; (h) ion selectivity is pH independent between 3 and 10, but (i) activity is reversibly lost at high pH; (j) methyl ester derivatives are fully active; N-acetyl and N-succinyl derivatives are inactive; (k) current-voltage characteristic is nonlinear when membrane separates nonidentical salt solutions. These characteristics are contrasted with those of valinomycin. Observations (a)–(g) suggest that aggregates of polyene and sterol from opposite sides of the membrane interact to create aqueous pores; these pores are not static, but break up (melt) and reform continuously. Mechanism of anion selectivity is obscure. Observations (h)–(j) suggest—NH3 + is important for activity; it is probably not responsible for selectivity, particularly since four polyene antibiotics, each containing two—NH3 + groups, induce ideal cation selectivity. Possibly the many hydroxyl groups in nystatin and amphotericin B are responsible for anion selectivity. The effects of polyene antibiotics on thin lipid membranes are consistent with their action on biological membranes.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andreoli T. E., Monahan M. The interaction of polyene antibiotics with thin lipid membranes. J Gen Physiol. 1968 Aug;52(2):300–325. doi: 10.1085/jgp.52.2.300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andreoli T. E., Tieffenberg M., Tosteson D. C. The effect of valinomycin on the ionic permeability of thin lipid membranes. J Gen Physiol. 1967 Dec;50(11):2527–2545. doi: 10.1085/jgp.50.11.2527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bean R. C., Shepherd W. C., Chan H. Permeability of lipid bilayer membranes to organic solutes. J Gen Physiol. 1968 Sep;52(3):495–508. doi: 10.1085/jgp.52.3.495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cass A., Finkelstein A. Water permeability of thin lipid membranes. J Gen Physiol. 1967 Jul;50(6):1765–1784. doi: 10.1085/jgp.50.6.1765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. DEMEL R. A., VAN DEENENL PENETRATION OF LIPID MONOLAYERS BY POLYENE ANTIBIOTICS. CORRELATION WITH SELECTIVE TOXICITY AND MODE OF ACTION. J Biol Chem. 1965 Jun;240:2749–2753. [PubMed] [Google Scholar]
  6. Finkelstein A., Cass A. Effect of cholesterol on the water permeability of thin lipid membranes. Nature. 1967 Nov 18;216(5116):717–718. doi: 10.1038/216717a0. [DOI] [PubMed] [Google Scholar]
  7. Hanai T., Haydon D. A. The permeability to water of bimolecular lipid membranes. J Theor Biol. 1966 Aug;11(3):370–382. doi: 10.1016/0022-5193(66)90099-3. [DOI] [PubMed] [Google Scholar]
  8. Holz R., Finkelstein A. The water and nonelectrolyte permeability induced in thin lipid membranes by the polyene antibiotics nystatin and amphotericin B. J Gen Physiol. 1970 Jul;56(1):125–145. doi: 10.1085/jgp.56.1.125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Huang C., Thompson T. E. Properties of lipid bilayer membranes separating two aqueous phases: water permeability. J Mol Biol. 1966 Feb;15(2):539–554. doi: 10.1016/s0022-2836(66)80126-2. [DOI] [PubMed] [Google Scholar]
  10. Kinsky S. C., Luse S. A., Zopf D., van Deenen L. L., Haxby J. Interaction of filipin and derivatives with erythrocyte membranes and lipid dispersions: electron microscopic observations. Biochim Biophys Acta. 1967;135(5):844–861. doi: 10.1016/0005-2736(67)90055-7. [DOI] [PubMed] [Google Scholar]
  11. LUCY J. A. GLOBULAR LIPID MICELLES AND CELL MEMBRANES. J Theor Biol. 1964 Sep;7:360–373. doi: 10.1016/0022-5193(64)90080-3. [DOI] [PubMed] [Google Scholar]
  12. MUELLER P., RUDIN D. O., TIEN H. T., WESCOTT W. C. Reconstitution of cell membrane structure in vitro and its transformation into an excitable system. Nature. 1962 Jun 9;194:979–980. doi: 10.1038/194979a0. [DOI] [PubMed] [Google Scholar]
  13. Mueller P., Rudin D. O. Action potentials induced in biomolecular lipid membranes. Nature. 1968 Feb 24;217(5130):713–719. doi: 10.1038/217713a0. [DOI] [PubMed] [Google Scholar]
  14. Mueller P., Rudin D. O. Development of K+-Na+ discrimination in experimental bimolecular lipid membranes by macrocyclic antibiotics. Biochem Biophys Res Commun. 1967 Feb 21;26(4):398–404. doi: 10.1016/0006-291x(67)90559-1. [DOI] [PubMed] [Google Scholar]
  15. Mueller P., Rudin D. O. Resting and action potentials in experimental bimolecular lipid membranes. J Theor Biol. 1968 Feb;18(2):222–258. doi: 10.1016/0022-5193(68)90163-x. [DOI] [PubMed] [Google Scholar]
  16. Pressman B. C., Harris E. J., Jagger W. S., Johnson J. H. Antibiotic-mediated transport of alkali ions across lipid barriers. Proc Natl Acad Sci U S A. 1967 Nov;58(5):1949–1956. doi: 10.1073/pnas.58.5.1949. [DOI] [PMC free article] [PubMed] [Google Scholar]

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