ON THE ONE-SIDED ACTION OF AMPHOTERICIN-B ON LIPID BILAYER-MEMBRANES

The one-sided action of tile polyene antibiotic, amphotericin B, on ph ospholipid bilayer membranes formed from synthetic phosphatidylcholine s (DOPC and DPhPC) and sterols (ergosterol and cholesterol), has been investigated. We found formation of well-defined ionic channels for bo th sterols and not only for ergosterol-containing membranes (Bolard, J ., P. Legrand, F. Heitz, and B. Cybulska. 1991. Biochemistry. 30:5707- 5715). Characteristics of these channels were studied in the presence of different salts. It was found that the channels have comparable con ductances but different lifetimes that are similar to 100-fold less in cholesterol-containing membranes than in ergosterol-containing ones. Channel blocking by tetraethylammonium (TEA) ions shows that TEA block age of channels in the presence of cholesterol increases their Lifetim es in analogy to the lengthening of lifetimes of protein channels bloc ked by local anesthetics (Neher, E., and J. H. Steinbach. 1978. J. Phy siol. 277:153-176). However, the effect of the blocker on single-chann el conductance is very close for both sterols. The data support the cl assical model of amphotericin B pore formation from complexes initiall y lying on the membrane surface as nonconducting prepores. We explain the antibiotic's cytotoxic selectivity by differences in the lifetimes of tile channels formed with different sterols and suggest that phosp hatidylcholine-sterol membranes can be used as a tool for rapid estima tion of polyene antibiotic cytotoxicity.