title: pH regulation of amphotericin B channels activity in the bilayer lipid membrane.
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.
  
  
  OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Our data indicated that extracellular acidity can reduce AmB activity.
authors.affiliation: Department of Physiology, Faculty of Medicine, International Branch of Shahid Behshti University of Medical Sciences, Shemiranat, Tehran, Iran.
authors.forename: Tahereh
authors.initials: T
authors.lastname: Shahmoradi
authors.affiliation: Neuroscience Research Center, Golestan University of Medical Sciences, Gorgan, Golestan, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Sepehry
authors.affiliation: Department of Physiology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Mazandaran, Iran.
authors.forename: Manuchehr
authors.initials: M
authors.lastname: Ashrafpour
keywords: Amphotericin B; bilayer lipid membrane; phosphatidylcholine; single channel recording