Formation of a leakage-type ion pathway in lipid bilayer membranes by divalent cationic cyanine dyes in cooperation with inorganic phosphate. Role of the cyanine dye in uncoupling of oxidative phosphorylation.

Divalent cationic cyanine dyes, such as 2,2'-[3-[2-(3-butyl-4-methyl-2-thiazoline-2-ylidene)-ethylidene] propenylene]bis[3-butyl-4-methylthiazolinium iodide] and platonin induced large membrane current fluctuation when an electrical potential difference was applied across a planar phosphatidylserine bilayer membrane in medium containing inorganic phosphate (Pi). Without Pi, the dyes did not induce current fluctuation at concentrations of less than 30 microM. Noise analysis of current fluctuation indicated formation of a pathway for ion leakage. From measurements of the interfacial tension between oil and aqueous phases, and of water permeability across liposomal membranes, Pi was concluded to relax the phospholipid bilayer structure, resulting in great reduction in the concentration of the cyanine dye necessary for induction of the leakage-type pathway. In the presence of Pi, cationic ions such as tetrabutyl ammonium and tetraphenyl phosphonium did not induce the leakage-type pathway, although they had electrophoretic effects at high concentrations. These facts suggest that the mechanism of the uncoupling of oxidative phosphorylation by dicationic cyanine dyes in mitochondria is different from that of cationic uncouplers such as tetrabutyl ammonium ion.