Electrical conductivity, transfer of hydrogen ions in lipid bilayer membranes and uncoupling effect induced by pentachlorobenzenethiol (Pentachlorothiophenol)

Abstract

Pentachlorobenzenethiol (PCBT) has been considered an anomalous uncoupler. It was reported as active in mitochondria, but not effective in inducing electrical conductivity in lipid bilayer membranes. We have overcome the experimental difficulties associated with accurate determination of the induced conductivity. The main contributing factors to the difficulties, we discovered, are the photolability and the low solubility of the compound in aqueous medium. We have conclusively demonstrated that PCBT does induce conductivity in lipid bilayers and compared this conductance with its uncoupling activity reported by other investigators in the literature. We present the results of steady-state current-voltage measurements: conductance dependence on applied voltage for various values of pH, buffer strength and PCBT concentration, as well as the dependence of the conductance on pH, buffer strength and PCBT concentration in the limit of zero applied voltage. We have also compared the above results with those obtained previously with pentachlorophenol. Our experimental results on PCBT-induced membrane conductance suggest that PCBT belongs to class II uncouplers and that "disulfide dimer" of PCBT is membrane inactive. Thus the replacement of oxygen in molecular structure of pentachlorophenol (R-OH) by sulfur (R-SH) does not change the protonophoretic activity of the compound. The conductivity of a membrane is due to PCBT-induced hydrogen ion transfer and it was found to be limited by the kinetics of reactions coupled to transmembrane charge transfer.(ABSTRACT TRUNCATED AT 250 WORDS)

Proton conductance caused by long-chain fatty acids in phospholipid bilayer membranes

“…Apparently, the bulk lipid tours around the membrane acts as a source for the replacement of long-chain fatty acids, which slowly diffuse out of the membrane. Similar behavior has been observed for other hydrophobic weak acids in planar bilayers [69]. Figure 4 shows that phloretin (4-100 ~M) inhibited the Gr~ produced by fatty acids.…”

Passive Permeability of Planar Lipid Bilayers to Organic Anions

“…Anionic permeability data were collected from literature for validation. The list (see Results and Discussion) makes no claim to completeness, and data of experiments that did not meet our above stated specifications of permeability were excluded: if UWL effects occurred or could not be ruled out (23,46), or if the permeability was dominated by dimer permeation (17,23,47,48), the data were not taken into account. If stated, permeability values were directly adopted.…”

“…In the past, there have been a multitude of electrophysiological experiments on the conductivity of planar lipid bilayers in the presence of weak acids or permanent ions (e.g., (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)). Still, the collection of a diverse data set on ionic membrane permeability from literature as a basis for a sound mechanistic understanding and a predictive model remains quite difficult.…”

EFFECTS OF HARDNESS, ALKALINITY AND pH ON THE TOXICITY OF PENTACHLOROPHENOL TO SELENASTRUM CAPRICORNUTUM (PRINTZ)

“…Moreland and Hilton [19] classify PCP as an inhibitory uncoupler, recognizing that its sites of action are several, including photophosphorylation, protein synthesis and lipid biosynthesis [20]. The mechanism(s) of PCP's toxicity remains to be precisely defined, but current evidence points to the disruption of membrane function [16,17,21].…”