A selective cholesterol-dependent induction of H+/OH- currents in phospholipid vesicles by amphotericin B.
The effect of amphotericin B on the proton/hydroxide permeability of small unilamellar vesicles has been investigated by using potential-dependent paramagnetic probes. Amphotericin B at 1-10 molecules/vesicle causes a modest 4-8-fold increase in the background H+/OH- permeability of egg phosphatidylcholine (egg PC) vesicles. However, in the presence of cholesterol, amphotericin B promotes a dramatic increase in the H+/OH- permeability of more than 2 orders of magnitude. Surprisingly, this is not observed in vesicle membranes containing ergosterol. In membranes composed of 5-15 mol% ergosterol, amphotericin B is even less effective at promoting H+/OH- currents than in pure egg PC vesicles. The K+ current promoted by amphotericin B in vesicles formed from egg PC and from egg PC plus cholesterol or ergosterol was measured. No significant sterol dependence was found for the K+ current. These results strongly suggest that different mechanisms, or amphotericin B/sterol complexes, are responsible for the induction of H+/OH- and K+ currents. These results have important implications for understanding the therapeutic and toxic effects of amphotericin B.
Hartsel
S C
SC
Department of Chemistry, University of Virginia, Charlottesville 22901.
Perkins
W R
WR
McGarvey
G J
GJ
Cafiso
D S
DS
D000666:Amphotericin B; D002784:Cholesterol; D006878:Hydroxides; D008081:Liposomes; D008954:Models, Biological; D010713:Phosphatidylcholines; D011522:Protons
D006878:Hydroxides; D008081:Liposomes; D010713:Phosphatidylcholines; D011522:Protons; D000666:Amphotericin B; D002784:Cholesterol