The effect of uncouplers of oxidative phosphorylation on lipid bilayer membranes: Carbonylcyanidem-chlorophenylhydrazone

Summary Detailed experimental data for conductivity and membrane potentials are presented for lecithin/cholesterol/decane bilayers in the presence of the uncoupler carbonylcyanidem-chlorophenylhydrazone (CCCP). These compare favorably with a theoretical model derived to explain the mechanism of action of uncouplers on bilayers. The model assumes that the weak acid uncoupler HA and its anion A⁻ are the sole species which permeate the membrane. Its key feature is the recognition of the existence of unstirred aqueous layers on either side of the membrane. The model accounts for, among other things, a maximum in the transmembrane conductivity at a pH to the alkaline side of the uncoupler pK _a and saturating current-voltage characteristics at high pH, both phenomena being found for CCCP. From a quantitative fit of model to data, values of 2.0×10⁻³ and 11 cm/sec are deduced for the permeability coefficients of the CCCP anion and the undissociated CCCP molecule, respectively.