One of the classic model compounds for membrane ion channel permeation is Amphotericin B, although the structure of the channel is still unknown. This polyene macrolide is thought to form ion permeable pores in lipid membranes by organizing into a barrel stave like arrangement of molecules with the polar polyol region in the middle. However, the size and nature of the channels seem to vary depending upon which sterol, ergosterol or cholesterol, is present in the phospholipid membrane. The supramolecular structure of such channels may be revealed by studying its ion permeation properties, especially the selectivity sequence of related ions (e.g. the alkali metal series). The three basic goals for this research are: 1)Obtain complete Group IA and IIA metal cation and halide selectivity sequences for Amphotericin channels in different phospholipid and sterol membrane environments, 2) Determine the temperature dependence, aggregation state and molecularity of channel formation in these environments, 3) Using these data in conjunction with electrostatic molecular modeling software, design consistent models for Amphotericin channel structures. %%% Biological membrane ion channels play a central role in many processes from neurotransmission to cystic fibrosis. This research should advance on knowledge of Amphotericin channels and ion channels in general.
