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. 2016 Jan-Jun;7(1):85-8.
doi: 10.4103/0976-9668.175082.

pH regulation of amphotericin B channels activity in the bilayer lipid membrane

Tahereh Shahmoradi  1 , Hamid Sepehry  2 , Manuchehr Ashrafpour  3
Affiliations

pH regulation of amphotericin B channels activity in the bilayer lipid membrane

Tahereh Shahmoradi et al. J Nat Sci Biol Med. 2016 Jan-Jun.

Abstract

Background: Amphotericin B (AmB) is a polyene antibiotic frequently applied in the treatment of systemic fungal infections in spite of its secondary effects. The pH plays a crucial role in modulating biophysical features of ion channels in the bilayer lipid membranes.

Aim: In this study, the role of pH in the regulation of AmB channel was assessed by single channel recording of ion channel incorporated in the artificial membrane.

Materials and methods: Bilayer lipid membrane was formed by phosphatidylcholine in a 350 μm diameter aperture between two chambers, cis and trans contained 200/50 mMKCl solutions, respectively; then AmB was incorporated into the bilayer lipid membrane. Single channel recordings were used to indicate the effects of pH changes on AmB channels activity. The records were analyzed by Clamp fit 10 software.

Results: A kinetic analysis of single channel currents indicated a cation ion channel with 500 pS conductance and voltage-dependence of the open probability of the AmB channel (P o). A reduction of cis pH to 6 decreased P o and conductance. This effect was also voltage-dependent, being greater at a more positive above -40. The pH changes in the range of 6-8 had no effect on the reversal potential and ion selectivity.

Conclusion: Our data indicated that extracellular acidity can reduce AmB activity.

Keywords: Amphotericin B; bilayer lipid membrane; phosphatidylcholine; single channel recording.

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Figures

Figure 1
Figure 1
Typical current recordings of single ion channels formed by amphotericin B in phosphorylcholine bilayer membranes measured at different potential when the membrane-cis solutions were buffered to various pH values (at column width)
Figure 2
Figure 2
Current-voltage relationships for single channel recordings, in asymmetrical KCl (200 mM) in the cis side and 50 mM KCl in the trans side when the membrane-cis solutions were buffered to pH 6, 7, and 8). Each point represents the means ± standard error of the mean of six different experiments (at column width)
Figure 3
Figure 3
Channel open probability (Po) at different voltages. When the membrane cis solutions were buffered to pH 6, 7, and 8 (at column width)
See this image and copyright information in PMC

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References

    1. Hartsel S, Bolard J. Amphotericin B: New life for an old drug. Trends Pharmacol Sci. 1996;17:445–9. - PubMed
    1. Brajtburg J, Powderly WG, Kobayashi GS, Medoff G. Amphotericin B: Current understanding of mechanisms of action. Antimicrob Agents Chemother. 1990;34:183–8. - PMC - PubMed
    1. Roethl E, Gassner M, Krenn BM, Romanovskaya-Romanko EA, Seper H, Romanova J, et al. Antimycotic-antibiotic amphotericin B promotes influenza virus replication in cell culture. J Virol. 2011;85:11139–45. - PMC - PubMed
    1. Schaffner CP, Plescia OJ, Pontani D, Sun D, Thornton A, Pandey RC, et al. Anti-viral activity of amphotericin B methyl ester: Inhibition of HTLV-III replication in cell culture. Biochem Pharmacol. 1986;35:4110–3. - PubMed
    1. Valeriote F, Medoff G, Dieckman J. Potentiation of anticancer agent cytotoxicity against sensitive and resistant AKR leukemia by amphotericin B1. Cancer Res. 1979;39(6 Pt 1):2041–5. - PubMed

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