Na+, K+ and Cl? selectivity of the permeability pathways induced through sterol-containing membrane vesicles by amphotericin B and other polyene antibiotics

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 intercationic 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 x 10(-7) M, the sequence determined for sterol-free small unilamellar vesicles (SUV) and cholesterol-containing SUV and LUV, Na+ > K+ > Rb+ > or = Cs+ > Li+ (sulfate salts), corresponded closely to Eisenman selectivity sequence number VII. At 5 x 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 x 10(-7) M, smaller with AmB, nil with AmE and N FruAmB. The selectivities observed were antibiotic, concentration and time dependent, which confirms the existence of different types of channels.

Amphotericin B Resistance and Membrane Fluidity in Kluyveromyces lactis Strains

“…AmB was used at subinhibitory doses (10 and 125 mg/liter for K. lactis and the K. lactis mutant, respectively). differentiated by their diameter (1,6,12). At low AmB concentrations, similar to those used in our study, the formation of channels with a low diameter induces a transitory high permeability for water and a loss of K ϩ and Mg 2ϩ (17).…”

Allicin enhances the oxidative damage effect of amphotericin B against Candida albicans

“…Although AmB is the gold standard of antifungal treatment for the most severe invasive mycoses, adverse effects are common, with nephrotoxicity being the most serious, occurring early in the course of treatment [4][5][6]33,20]. The severe side effects restrict AmB clinical application and this has increased the interest in using drug combinations to enhance its efficacy in order to reduce the dose of AmB required for therapy and thus lessen the severity of side effects.…”

It only takes one to do many jobs: Amphotericin B as antifungal and immunomodulatory drug

“…Moreover, they participate differentially in the killing effect of the molecule [see seminal review in Cohen (2010) and Hartsel et al (1994); Romero et al (2009)]. After addition of AmB to the cells, the first type of pores that are formed are non-aqueous, which are permeable to monovalent cations and have lower permeability to monovalent anions (Ramos et al, 1996; Romero et al, 2009).…”