Large-conductance cholesterol-amphotericin B channels in reconstituted lipid bilayers.
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.
Yilma
Solomon
S
Department of Anatomy, Physiology and Pharmacology, Auburn University, 109 Greene Hall, Auburn, AL 36849, USA.
Cannon-Sykora
Jennifer
J
Samoylov
Alexandre
A
Lo
Ting
T
Liu
Nangou
N
Brinker
C Jeffrey
CJ
Neely
William C
WC
Vodyanoy
Vitaly
V
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*
D000935:Antifungal Agents; D007473:Ion Channels; D008051:Lipid Bilayers; D000666:Amphotericin B; D002784:Cholesterol