On the role of sterol in the formation of the amphotericin B channel

Abstract

Amphotericin B is an antimycotic agent that has been studied for a long time, both because of its pharmacological action and the interest in understanding how this ionic channel works. It has been proposed that the channel is formed by a barrel of monomers, and that the presence of sterol is needed for the formation of such a barrel. As a matter of fact this need Bf a sterol has been used as a guiding idea in attemps to design derivatives more efficient in the discrimination of the cholesterol containing membranes, as compared to the ergosterol containing ones, henceforth diminishing the unwanted side effects ih its pharmacological use. In this work we show that unitary channels that appear in a cholesterol containing membrane also appear when this membrane is free of cholesterol. We prove this to be the case for two membranes, a biological one, asolectin, and a synthetic one, DMPC. We then advance the idea that the role of sterols in the formation of the amphotericin B channel is related to the effects they have on the structure of the membrane itself, rather than to a direct involvement in the channel formation. We further look into the effect that different cholesterol concentrations in the membrane produce on: the single channel properties. (C) 1998 Elsevier Science B.V. All rights reserved.