Ion channel behavior of amphotericin B in sterol-free and cholesterol- or ergosterol-containing supported phosphatidylcholine bilayer model membranes investigated by electrochemistry and spectroscopy.
Amphotericin B (AmB) is a popular drug frequently applied in the treatment of systemic fungal infections. In the presence of ruthenium (II) as the maker ion, the behavior of AmB to form ion channels in sterol-free and cholesterol- or ergosterol-containing supported phosphatidylcholine bilayer model membranes were studied by cyclic votammetry, AC impedance spectroscopy, and UV/visible absorbance spectroscopy. Different concentrations of AmB ranging from a molecularly dispersed to a highly aggregated state of the drug were investigated. In a fixed cholesterol or ergosterol content (5 mol %) in glassy carbon electrode-supported model membranes, our results showed that no matter what form of AmB, monomeric or aggregated, AmB could form ion channels in supported ergosterol-containing phosphatidylcholine bilayer model membranes. However, AmB could not form ion channels in its monomeric form in sterol-free and cholesterol-containing supported model membranes. On the one hand, when AmB is present as an aggregated state, it can form ion channels in cholesterol-containing supported model membranes; on the other hand, only when AmB is present as a relatively highly aggregated state can it form ion channels in sterol-free supported phosphatidylcholine bilayer model membranes. The results showed that the state of AmB played an important role in forming ion channels in sterol-free and cholesterol-containing supported phosphatidylcholine bilayer model membranes.
Huang
Weimin
W
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China.
Zhang
Zheling
Z
Han
Xiaojun
X
Tang
Jilin
J
Wang
Jianguo
J
Dong
Shaojun
S
Wang
Erkang
E
D000666:Amphotericin B / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry; D017097:Electric Impedance; D004563:Electrochemistry / Q000379:methods; D004875:Ergosterol / Q000737:chemistry; D007473:Ion Channels / Q000737:chemistry*; D008051:Lipid Bilayers; D046911:Macromolecular Substances; D008564:Membrane Potentials; D008567:Membranes, Artificial; D010713:Phosphatidylcholines / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013057:Spectrum Analysis / Q000379:methods; D013261:Sterols / Q000737:chemistry*
D007473:Ion Channels; D008051:Lipid Bilayers; D046911:Macromolecular Substances; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; D013261:Sterols; D000666:Amphotericin B; D002784:Cholesterol; D004875:Ergosterol