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Updated: Mar 23, 2026
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Published on: October 13, 2010
pH regulation of amphotericin B channels activity in the bilayer lipid membrane
Tahereh Shahmoradi1, Hamid Sepehry2, Manuchehr Ashrafpour3
1Department of Physiology, Faculty of Medicine, International Branch of Shahid Behshti University of Medical Sciences, Shemiranat, Tehran, Iran.
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.
Insights
Extracellular acidity reduces amphotericin B (AmB) channel activity by decreasing its open probability and conductance. This pH-dependent regulation of AmB channels is crucial for understanding its efficacy in treating fungal infections.
Area of Science:
- Biophysics
- Membrane Biology
- Pharmacology
Background:
- Amphotericin B (AmB) is a key antifungal antibiotic.
- Its efficacy is limited by side effects.
- Ion channel function in lipid membranes is pH-sensitive.
Purpose of the Study:
- To investigate the role of pH in regulating Amphotericin B (AmB) ion channel activity.
- To assess the impact of pH on AmB channel biophysical properties.
Main Methods:
- Incorporation of AmB into a phosphatidylcholine bilayer lipid membrane.
- Single-channel recordings to monitor AmB channel activity.
- Analysis of channel kinetics and conductance using Clamp fit 10 software.
Main Results:
- AmB forms a cation channel with 500 pS conductance and voltage-dependent open probability (P o).
- Lowering cis pH to 6 significantly decreased P o and conductance.
- These effects were voltage-dependent and more pronounced at positive potentials.
Conclusions:
- Extracellular acidity reduces Amphotericin B (AmB) channel activity.
- pH is a critical regulator of AmB channel function.
- Understanding pH effects may optimize AmB therapy.
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