PHOTODYNAMIC INACTIVATION OF ION CHANNELS FORMED BY THE POLYENE ANTIBIOTIC AMPHOTERICIN-B IN LIPID-MEMBRANES

The polyene antibiotic amphotericin B forms ion channels in biological membranes. The nature of these channels has been characterized in art ificial lipid membranes. This model system has been used to investigat e the photodynamic inactivation of polyene channels, observed on illum ination of the membrane by visible light in the presence of the photos ensitizer rose bengal. Channel inactivation is detected via the decrea se in the ionic current flowing through the channels when a constant m embrane voltage is applied. The decrease, which extends over several o rders of magnitude, is due to a light-induced closing of individual ch annels. Direct evidence of channel closing is provided by the observat ion of discrete current steps at sufficiently small numbers of channel s inside the membrane. In addition to electrical measurements, photody namic damage is studied via the investigation of the characteristic ch anges of the absorption spectrum of amphotericin B adsorbed to liposom es. It is suggested that channel inactivation is due to a peroxidation process of the polyene part of the molecule, which gives rise to a de stabilization of the pore-forming aggregates of amphotericin B. (C) 19 97 Elsevier Science S.A.