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 artificial lipid membranes. This model system has been used to investigate the photodynamic inactivation of polyene channels, observed on illumination of the membrane by visible light in the presence of the photosensitizer rose bengal. Channel inactivation is detected via the decrease in the ionic current flowing through the channels when a constant membrane voltage is applied. The decrease, which extends over several orders of magnitude, is due to a light-induced closing of individual channels. Direct evidence of channel closing is provided by the observation of discrete current steps at sufficiently small numbers of channels inside the membrane. In addition to electrical measurements, photodynamic damage is studied via the investigation of the characteristic changes of the absorption spectrum of amphotericin B adsorbed to liposomes. It is suggested that channel inactivation is due to a peroxidation process of the polyene part of the molecule, which gives rise to a destabilization of the pore-forming aggregates of amphotericin B. (C) 1997 Elsevier Science S.A.