Inactivation by ionizing radiation of ion channels formed by polyene antibiotics amphotericin B and nystatin in lipid membranes: an inverse dose-rate behavior

Abstract

The phenomena reported are part of a study about the effects of ionizing radiation on membrane transport. We found that the conductance of lipid membranes in the presence of the polyene-antibiotics nystatin or amphotericin B is reduced to virtually zero following irradiation. Ion channels formed by these substances seem to represent extremely sensitive structures being inactivated by radiation doses in the range of a few Centigray (1 cGy = 1 rad) at sufficiently small dose rates. Inactivation shows a so-called inverse dose-rate behavior, i.e., at constant radiation dose the effect increases with decreasing dose rate. Similar to radiation-induced lipid peroxidation the phenomenon may be understood on the basis of a radical chain mechanism initiated by free radicals of water radiolysis. The process--via peroxidation of the polyene part of the molecules--is suggested to modify the hydrophobic exterior and to destabilize the barrel-like structure of the ion channels.