Influence of cations on the mode of action of miconazole on yeast cells

The influence of the antifungal agent miconazole nitrate on yeast plasma membranes was studied in a concentration range 0-100 microM. The reaction of 100 microM miconazole with the plasma membranes lead to a rapid breakdown of the transmembrane pH gradient and to an efflux of metabolites from the cytoplasm of the cells. This effect of miconazole could be reversed by mono-, di- and most effectively by trivalent cations due to the formation of miconazole-cation complexes. At a ratio of trivalent cation/miconazole (1:3) the effect was completely reversed. X-Ray diffraction studies indicated a crystalline structure of the aluminium-miconazole complex.