Amphotericin B and Nystatin Show Different Activities on Sterol-free Vesicles

It has generally been assumed that the polyene antibiotics Nystatin and Amphotericin B cause membrane damage by the same mechanism. However, using kinetic fluorescence methods we have found that AmB and Nystatin have very different activities on sterol-free dioleoyl phosphatidylcholine and egg phosphatidylcholine small unilamellar vesicles. At very low AmB concentrations (less than 1/1000 lipids in egg phosphatidylcholine) significant K+ permeability enhancement is observed. However, even at very high Nystatin to lipid ratios (1/100) very little K+ current is induced, particularly in dioleoyl phosphatidylcholine vesicles. The novel technique described here uses a K+/H+ exchange mechanism to detect minute transmembrane K+ currents by monitoring internal membrane vesicle pH changes with pyranine.