Weak-acid uncouplers of oxidative phosphorylation. Mechanism of action on thin lipid membranes

Weak-acid uncouplers of oxidative phosphorylation such as p-trifluoromethoxycarbonylcyanidephenylhydrazone, tetrachloro-2-trifluoromethylbenzimidazole, m-chlorocarbonylcyanidephenylhydrazone, and 2,4-dinitrophenol can increase the conductance of thin lipid membranes by several orders of magnitude. In this high conductance state these membranes appear to be ideally selectively permeable to H⁺ or OH^-. We suggest, however, that the primary charge carrier in the membrane is neither H⁺ or OH^-, but rather a dimer formed between the undissociated and dissociated form of the weak acid, and we show that all of the data on the action of these weak acids on thin lipid membranes are consistent with this picture.