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Summary. The purpose of the work presented in this paper was to determine experimentally the actual mechanism of lipid bilayer conductivity in the presence of tetrachlorotrifluoromethylbenzimidazole (TTFB). The capacitance and conductance of lipid bilayers were measured with a current-clamp method, as a function of equal TTFB concentrations (10 -7 to 5 • 10-5 M) in the two aqueous phases. The voltage across the membrane was measured as a function of time during rectangular current pulses. If the hydrogen buffer capacity of the solution is low, the voltage response to long current pulses has two components. Tile slow component is due to hydrogen ion concentration changes in the unstirred layers. This component disappears if the buffer capacity is made high enough. Membrane capacitance and conductance can be determined from the fast component of the voltage response. The conductance increases with the square of TTFB concentration (pH 2 to 7) and the capacitance is 0.4 laF/cm 2 for the range of concentration used. If solutions of low buffer capacity are used, shifts of hydrogen ion concentrations near the membrane give rise to a complicated dependence of the membrane potential on pH given a unit pH difference between the two aqueous solutions (protonic potential). This dependence can be explained if the membrane permeability for neutral uncoupler molecules (TH) is high enough. The membrane permeability coefficient is determined: PTn= 10 cm/sec, in other experiments the dependence of short-circuit current on pH difference between the two solutions was also measured, with the pH value on one side fixed in a given experiment. These complicated nonmonotonic dependences can be described using a mathematical equation with only two parameters: (1) the dissociation constant of TTFB in water (pK=5.2), and (2) the proportionality factor between short-circuit current and TTFB concentration squared. These data can be formally interpreted to mean that the membrane is permeable only to TzHand TH, where T is TTFB anion and H is hydrogen ion. However, this model does not explain the high current values obtained because of the limited rate constant of T2H-formation in aqueous solution. An alternative model is proposed. It is shown that the T2H-is not formed in aqueous phase but rather within the membrane. The TzH-can be the intramembrane charge carrier if its life-time is long enough. If the average lifetime is short, current might be carried through the membrane by proton exchange between TH and T-, when they collide. This mechanism could also account for the action of uncouplers of oxidative phosphorylation other than TTFB.

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A molecular model of ionic channel formed by flexible molecules of amphotericin B and cholesterol is proposed. Complexes with axial symmetry from 5 to 11 were simulated. In contrast to the model of the channel formed from rigid molecules, flexible molecules form a tightly packed structure consolidated by both dispersive forces and intermolecular hydrogen bonds. Contributions of a lactone ring, polar heads, cholesterol and lipid environments to the global energy of the complex formation are discussed. Among the complexes capable of ionic transport, that of axial symmetry eight is preferable. Two types of complexes, differing by the number of intramolecular hydrogen bonds, are shown to be possible.

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