Ion selectivity, transport properties and dynamics of amphotericin B channels studied over a wide range of acidity

Alina Asandei1, Tudor Luchian

  • 1Alexandru I. Cuza University, Faculty of Physics, Laboratory of Biophysics & Medical Physics, Boulevard King Carol I, No. 11, Iasi, R-700506, Romania.

Insights

Amphotericin B (AmB) channel selectivity shifts from anion to cation selective with increasing pH due to ionization changes. Ionic conductance varies non-monotonically with pH, influenced by membrane potential, impacting antifungal drug transport.

Area of Science:

  • Biophysics
  • Membrane Transport
  • Antifungal Drug Research

Background:

  • Amphotericin B (AmB) is a vital antifungal antibiotic for systemic infections.
  • Its use is limited by severe side effects.
  • Understanding AmB channel properties is crucial for optimizing its therapeutic application.

Purpose of the Study:

  • Investigate the influence of pH on Amphotericin B (AmB) channel selectivity and transport.
  • Elucidate the mechanisms behind pH-dependent channel behavior.
  • Explore AmB channel rectification and insertion properties.

Main Methods:

  • Electrophysiology experiments on single and multiple AmB channels.
  • Utilized reconstituted zwitterionic lipid membranes with ergosterol.
  • Performed measurements at varying pH values (2.8, 7, and 11).

Main Results:

  • AmB channels exhibited anion selectivity at pH 2.8 and cation selectivity at neutral/alkaline pH.
  • Single-molecule ionic conductance showed non-monotonic pH dependence.
  • AmB channels displayed strong rectification and favored insertion under positive potentials at low pH.

Conclusions:

  • pH-dependent ionization of AmB molecule functional groups dictates channel selectivity.
  • Membrane surface and dipole potentials contribute to non-monotonic conductance changes.
  • Rectifying behavior and insertion preferences offer insights into AmB channel formation and function.

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