Abstract
Sodium-22 efflux was measured in multilamellar liposomes, exposed to one of the two polyene antibiotics amphotericin B or nystatin. Polyene mediated 22Na transport progressively rises with membrane sterol concentrations up to about 20 mol %, but falls with higher cholesterol concentrations. The polyene induced 22Na movement in cholesterol rich liposomes could be 'restored' by the addition of either dibucaine or propranolol (two local anesthetics) to the aqueous solution. These observations are interpreted in terms of the model of De Kruijff and Demel (Biochim. Biophys. Acta, 339, 57-70, 1974). In this model, nystatin and amphotericin B first complex with cholesterol and then these complexes aggregate to form transmembrane channels. It is here proposed that the aggregation of these complexes is inhibited by a high cholesterol content (decreased membrane fluidity) but that the two local anesthetics, by disrupting phospholipid-sterol interactions (increased membrane fluidity), can 'restore' this process of aggregation.
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