Resonance of Amphotericin B Channel Activity in Lipidic Membranes

Abstract

Amphotericin B (AmB) is a polyene molecule that forms pores consisting of several monomers of the molecule in a barrel configuration inserted in lipidic membranes. The molecular mechanism by which they are absorbed and then inserted, diffused and form a pore is not well known, but the aggregation in solution seems to affect the previous procedures. Therefore, AmB mode of action has been widely stuedied, i.e., channel activity dependance with sterols and lipid composition, transmembrane potential, temperature, phase diagram of the bilayer, etc. However, not much research has been done to study the channelas opening and closing frequencies which reflects the intrinsic dynamics of the channel. In previous works, e.g. Bezrukov [1], the existence of stocastic resonance of alamethicin channels has been shown. This suggests that a characteristic frequency could also exist for polyenes. In this work, the tip-dip technique was used to characterize the AmB channels dynamics in POPC and 30% mol Cholesterol membranes. For this, square trains of pulses of different frequencies were applied to the above membrane containing AmB. The results show the existence of a specific frequency of the train of pulses at which an increased activity of the channel is observed. This is important because it occurs in a non excitable system, suggesting that it could be a general effect; a physical characteristic of the peptidic or polyenic channels. Understanding this phenomena may shed light in those processes in which these molecules are involved.