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Optically black, thin lipid membranes prepared from sheep erythrocyte lipids have a high dc resistance (Rm
108 ohm-cm2) when the bathing solutions contain NaCl or KCl. The ionic transference numbers (Ti) indicate that these membranes are cation-selective (TNa
0.85; TCl
0.15). These electrical properties are independent of the cholesterol content of the lipid solutions from which the membranes are formed. Nystatin, and probably amphotericin B, are cyclic polyene antibiotics containing
36 ring atoms and a free amino and carboxyl group. When the lipid solutions used to form membranes contained equimolar amounts of cholesterol and phospholipid, these antibiotics reduced Rm to
102 ohm-cm2; concomitantly, TCl became
0.92. The slope of the line relating log Rm and log antibiotic concentration was
4.5. Neither nystatin (2 x 10-5 M) nor amphotericin B (2 x 10-7 M) had any effect on membrane stability. The antibiotics had no effect on Rm or membrane permselectivity when the lipids used to form membranes were cholesterol-depleted. Filipin (10-5 M), an uncharged polyene with 28 ring atoms, produced striking membrane instability, but did not affect Rm or membrane ionic selectivity. These data suggest that amphotericin B or nystatin may interact with membrane-bound sterols to produce multimolecular complexes which greatly enhance the permeability of such membranes for anions (Cl-, acetate), and, to a lesser degree, cations (Na+, K+, Li+).
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S. Krasne, G. Eisenman, and G. Szabo Freezing and Melting of Lipid Bilayers and the Mode of Action of Nonactin, Valinomycin, and Gramicidin Science, October 22, 1971; 174(4007): 412 - 415. [Abstract] [PDF] |
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