title: Large-conductance cholesterol-amphotericin B channels in reconstituted lipid bilayers.
abstract: The antimycotic activity of amphotericin B (AmB) depends on its ability to make complexes sterols to form ion channels that cause membrane leakage. To study this phenomenon, surface pressure (pi) as a function of surface area (A) and pi-A hysteresis were measured in monolayers of AmB-cholesterol mixtures on the water-air interface. The most stable monolayers were produced from molecules of AmB and cholesterol with 2:1 stoichiometry. At this ratio, AmB and cholesterol interact to form ion channels in lipid bilayers with millisecond dwell times and conductances of 4-400 pS. The AmB-cholesterol complexes assemble in three, four, etc., subunit aggregates to form ion channels of diverse and large-conductances. Their I-V characteristics were linear over a range of +/-200 mV. The channel currents were inhibited by the addition of tetraethylammonium (TEA), potassium channel blocker, to the cis-side of the membrane. Likewise, AmB-cholesterol complexes reconstituted in membrane-coated nanoporous silicon dioxide surfaces showed single channel behavior with large amplitudes at various voltages. Large-conductance ion channels show great promise for use in biosensors on solid supports.
authors.affiliation: Department of Anatomy, Physiology and Pharmacology, Auburn University, 109 Greene Hall, Auburn, AL 36849, USA.
authors.forename: Solomon
authors.initials: S
authors.lastname: Yilma
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cannon-Sykora
authors.forename: Alexandre
authors.initials: A
authors.lastname: Samoylov
authors.forename: Ting
authors.initials: T
authors.lastname: Lo
authors.forename: Nangou
authors.initials: N
authors.lastname: Liu
authors.forename: C Jeffrey
authors.initials: CJ
authors.lastname: Brinker
authors.forename: William C
authors.initials: WC
authors.lastname: Neely
authors.forename: Vitaly
authors.initials: V
authors.lastname: Vodyanoy
mesh_terms: D000666:Amphotericin B / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000502:physiology; D002784:Cholesterol / Q000737:chemistry / Q000502:physiology*; D007473:Ion Channels / Q000737:chemistry / Q000502:physiology*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D007473:Ion Channels; D008051:Lipid Bilayers; D000666:Amphotericin B; D002784:Cholesterol