The effects of the macrotetralide actin antibiotics on the electrical properties of phospholipid bilayer membranes.

This paper, the last in a series of three, characterizes the electrical properties of phospholipid bilayer membranes exposed to aqueous solutions containing nonactin, monactin, dinactin, and trinactin and Li(+), Na(+), K(+), Rb(+), Cs(+), and NH 4 (+) ions. Not only are both the membrane resistance at zero current and the membrane potential at zero current found to depend on the aqueous concentrations of antibiotic and ions in the manner expected from the theory of the first paper, but also these measurements are demonstrated to be related to each other in the manner required by this theory for "neutral carriers". To verify that these antibiotics indeed are free to move as carriers of cations, cholesterol was added to the lipid to increase the "viscosity" of the interior of the membrane. Cholesterol decreased by several orders of magnitude the ability of the macrotetralide antibiotics to lower the membrane resistance; nevertheless, the permeability ratios and conductance ratios remained exactly the same as in cholesterolfree membranes. These findings are expected for the "carrier" mechanism postulated in the first paper and serve to verify it. Lastly, the observed effects of nonactin, monactin, dinactin, and trinactin on bilayers are compared with those predicted in the preceding paper from the salt-extraction equilibrium constants measured there; and a close agreement is found. These results show that the theory of the first paper satisfactorily predicts the effects of the macrotetralide actin antibiotics on the electrical properties of phospholipid bilayer membranes, using only the thermodynamic constants measured in the second paper. It therefore seems reasonable to conclude that these antibiotics produce their characteristic effects on membranes by solubilizing cations therein as mobile positively charged complexes.