Abstract
Membrane diffusion potentials induced by amphotericin B (AmB), amphotericin B methyl ester (AmE), N-fructosyl AmB (N FruAmB) and vacidin, an aromatic polyene antibiotic, in ergosterol- or cholesterol-containing egg yolk phosphatidylcholine large unilamellar vesicles (LUV), were measured in various media, in order to determine the relative selectivity of Na+, K+, Cl− and other ions in these environments. Changes in the membrane potential were followed by fluorescence changes of 3,3′-dipropylthiadicarbocyanine (diS-C3-(5)). Subtle changes in intercationic selectivity were monitored by measuring biionic potentials, using the fluorescent pH sensitive probe pyranine. In all the cases studied, the intereationic selectivity of the permeability pathways induced by the four antibiotics was weak compared to that of specific biological channels, though distinct differences were noted. With AmB the selectivity appeared to be concentration dependent. Above 5 × 10−7 M, the sequence determined for sterol-free small unilamellar vesicles (SUV) and cholesterol-containing SUV and LUV, Na+ > K+ > Rb+ ≥ Cs+ > Li+ (sulfate salts), corresponded closely to Eisenman selectivity sequence number VII. At 5 × 10−7 M and below the selectivity switched from Na+ > K+ to K+ > Na +. In contrast, Li+ was the most permeant ion for AmB channels in the presence of ergosterol. The selectivity between Na+ or K+ vs. Cl− varied with the antibiotic. It was very strong with vacidin at concentrations below 5 × 10−7 M, smaller with AmB, nil with AmE and N FruAmB. The selectivities observed were antibiotic, concentration and time de pendent, which confirms the existence of different types of channels.
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Abbreviations
- AmB:
-
amphotericin B
- AmE:
-
amphotericin B methylester
- BLM:
-
bilayer membranes
- DiSC3(5):
-
3,3′-dipropylthi-acarbocyanine iodide
- DMSO:
-
dimethylsulfoxide
- EPC:
-
egg yolk lecithin
- FCCP:
-
carbonyl cyanide p-trifluoro methoxyphenyl-hydrazone
- HEPES:
-
N-(2-hydroxyethylpiperazine)-N′-(2-ethanesulfonic acid)
- LUV:
-
large unilamellar vesicles
- MOPS:
-
3-(N-morpholino)propanesulfonic acid
- N-Fru AmB:
-
N(1-deoxy-D-fructos-1-yl) amphotericin B
- Oxonol V1:
-
bis(3-propyl-5-oxoisoazol-4yl)pentamethine oxonol
- SUV:
-
small unilamellar vesicles
References
Andreoli TE (1974) The structure and function of amphotericin B-cholesterol pores in lipid membranes. Ann NY Acad Sci 235:448–468
Apell HJ, Bersch B (1987) Oxonol VI as an optical indicator for membrane potential in lipid vesicles. Biochim Biophys Acta 903:480–494
Archer DB (1976) Effect of the lipid composition of mycoplasma mycoides subspecies capri and phosphatidylcholine vesicles upon the action of polyene antibiotics. Biochim Biophys Acta 864:68–76
Bolard J, Legrand Ph, Heitz F, Cybulska B (1991) One-sided action of amphotericin B on cholesterol-containing membranes is determined by its self-association in the medium. Biochemistry 30:5707–5715
Borisova M, Brutyan RA, Ermishkin LN (1986) Mechanism of anion-cation selectivity of amphotericin B channels. J Membrane Biol 90:13–20
Capuozzo E, Jullien S, Salerno C, Crifo C (1990) Inhibition of erythrocyte ghost ATPase by polyene antibiotics. Biochim Internat 20:1135–1139
Cohen BE (1986) Concentration- and time-dependence of amphotericin B induced permeability changes across ergosterol-containing liposomes. Biochim Biophys Acta 857:117–122
Cohen BE (1992) A sequential mechanism for the formation of aqueous channels by amphotericin B in liposomes. The effect of sterols and phospholipid composition. Biochim Biophys Acta 1108:49–58
Cybulska B, Ziminski T, Borowski E, Gary-Bobo CM (1983) Influence of electric charge of aromatic heptaene macrolide antibiotics on their activity on biological and lipidic model membranes. Mol Pharmacol 24:270–273
Cybulska B, Seksek O, Henry-Toulmé N, Czerwinski A, Bolard J (1992) Polyene macrolide antibiotics: indirect stimulation of the Na+/H+ exchanger of BALB/c B lymphoid cell line, A20. Biochem, Pharmacol 44:539–544
DeKruijff B, Gerritsen WJ, Oerlemans A, Demel RA, Van Deenen LLM (1974) Polyene antibiotic-sterol interactions in membranes of Acholeplasma laidlawii cells and lecithin liposomes. I. Specificity of the membrane permeability changes induced by polyene antibiotics. Biochim Biophys Acta 339:30–43
Deuticke B, Lütkemeier P, Sistemich M (1984) Ion selectivity of aqueous leaks induced in the erythrocyte membrane by crosslinking of membrane proteins. Biochim Biophys Acta 775:150–160
Falkowski L, Pawlak J, Zielinski J, Golik J, Troka E, Stefanska B, Jereczek E (1982) The structure of N-glycosyl derivatives of polyene macrolide antibiotics. The reaction of nystatin with D-glucose. Polish J Chem 56:123–130
Gary-Bobo CM, Cybulska B (1982) Cation permeability induced by 2 aromatic heptaenes, vacidin A and candicidin D on phospholipid unilamellar vesicles. J Antibiotics 35:1068–1071
Glaser R (1982) Echinocyte formation induced by potential changes of human red blood cells. J Membrane Biol 66:79–85
Hauser H, Phillips MC, Stubbs M (1972) Ion permeability of phospholipid bilayers. Nature 239:342–344
Hartsel SC, Perkins WR, McGarvey GJ, Cafiso DS (1988) A selective cholesterol dependent induction of H+/OH− currents in phospholipid vesicles by amphotericin B. Biochemistry 27:2656–2660
Hartsel SC, Benz SK, Peterson RP, Whyte BS (1991) Potassium-selective amphotericin B channels are predominant in vesicles regardless of sidedness. Biochemistry 30:77–82
Henry-Toulmé N, Séman M, Bolard J (1989a) Interaction of amphotericin B and its N-fructosyl derivative with murine thymocytes: a comparative study using fluorescent membrane probe. Biochim Biophys Acta 1051:245–252
Henry-Toulmé N, Bolard J, Hermier B, Séman M (1989b) Immunomodulating properties of the N-(1-deoxy-D-fructos-1-yl) derivative of amphotericin B in mice. Immunol Lett 20:63–66
Hsu Chen SC, Feingold DS (1973) Polyene antibiotic action on lecithin liposomes: effect of cholesterol and fatty acyl chains. Biochem Biophys Res Commun 51:972–978
Klemberg ME, Finkelstein A (1984) Single-length and double length channels formed by nystatin in lipid bilayer membranes. J Membrane Biol 80:257–269
Lambing HE, Wolf BD, Hartsel SC (1993) Temperature effects on the aggregation state and activity of amphotericin B. Biochim Biophys Acta 1152:185–188
Legrand Ph, Romero EA, Cohen E, Bolard J (1992) Effects of aggregation and solvent on the toxicity of amphotericin B to human erythrocytes Antimicrob. Agents Chemother 36:2518–2522
Loew LM, Benson L, Lazrovici P, Rosenberg I (1985) Fluorimetric analysis of transferable membrane pores. Biochemistry 24:2101–2104
Mechlinksi CP, Schaffner W (1972) Polyene macrolide derivatives. I N-acylation and esterification reactions with amphotericin B. J Antibiotics XXV: 256–258
Marty A, Finkelstein A (1975) Pores formed in lipid bilayer membranes by nystatin. Differences in its one-sided and two-sided action. J Gen Phys 65:515–526
Mickus DE, Levitt DG, Rychnovsky SD (1992) Enantiomeric cholesterol as a probe of ion-channel structure. J Am Chem Soc 114:359–360
Polymeropoulos EE, Brickman J (1985) Annu Rev Biophys Chem 14:315–330
Sambasivarao D, Rao NM, Sitaramam V (1986) Anomalous permeability and stability characteristics of erythrocytes in non-electrolyte media. Biochim Biophys Acta 857:48–60
Schaffner CP (1984) Polyene macrolides in clinical practice: pharmacology and other adverses effects. In: Macrolides antibiotics, chemistry, biology and practice. Omura S (ed) Academic Press, London, pp 457–469
Schell RE, Tran NV, Bramhall S (1989) Amphotericin B-induced changes in renal membrane permeation: a model of nephrotoxicity. Biochem Biophys Res Commun 159:1165–1170
Surarit R, Shepherd MG (1987) The effects of azole and polyene antifungals on the plasma membrane enzymes of Candida albicans. J Med Vet Mycol 25:403–412
Szoka F, Papahadjopoulos D (1979) Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation. Proc Natl Acad Sci USA 75:4194–4198
Vertut-Croquin A, Bolard J, Chabbert M, Gary-Bobo CM (1983) Difference in the interaction of the polyene antibiotic amphotericin B with cholesterol- and ergosterol-containing phospholipid vesicles. A circular dichroism and permeability study. Biochemistry 22:2940–2944
Vertut-Doi A, Hannaert P, Bolard J (1988) The polyene antibiotic amphotericin B inhibits the Na+/K+ pump of human erythrocytes. Biochem Biophys Res Commun 157:692–697
Whyte BS, Peterson RP, Hartsel SC (1989) Amphotericin B and nystatin show different activities on sterol-free vesicles. Biochem Biophys Res Commun 164:609–614
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Hartsel, S.C., Benz, S.K., Ayenew, W. et al. Na+, K+ and Cl− selectivity of the permeability pathways induced through sterol-containing membrane vesicles by amphotericin B and other polyene antibiotics. Eur Biophys J 23, 125–132 (1994). https://doi.org/10.1007/BF00208866
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DOI: https://doi.org/10.1007/BF00208866