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PHOTOSENSITIZED MEMBRANE DAMAGE: SINGLE CHANNEL INACTIVATION AND LEAK CONDUCTANCE Lars Kunz and Günther Stark Department of Biology, University of Konstanz, D -78457 Konstanz, Germany Abstract Illumination of cellular membranes by visible light in the presence of appropriate photosensitizers is known to inactivate specific ionic pathways and to increase the leak conductance of the membranes. While previous studies have concentrated on the macroscopic ionic currents, the present study separates the two phenomena at the microscopic level. Using opossum kidney (OK) cells as epithelial model system and photofrin II as sensitizer, the patch-clamp technique in inside-out configuration has been applied to show the inactivation of single ion channels immediately after start of illumination and the subsequent strong increase of the leak conductance. Inactivation is shown for three kinds of channels: the large-conductance Ca2+-dependent K+ channel (maxi-KCa), the stretch-activated nonselective cation channel (SA-cat) and a small-conductance K+ channel (sK). The largely identical inactivation behaviour of the three channel types suggests a common mechanism which might be based on the interaction of products of photodynamically induced lipid peroxidation with the channel proteins. Lipid peroxidation is suggested to be also responsible for the increase of the leak conductance, which was found to be rather nonselective for small cations and anions. Both phenomena, the inactivation of specific ion channels and the increase of the unspecific leak conductance, contribute to the pronounced depolarization of the membrane potential observed experimentally. The ionic pathways of the leak conductance also allow permeation of Ca2+ ions. The resulting Ca2+ flux may lead to the photodynamically induced increase of the intracellular Ca2+ concentration observed in various cell lines.