A study on the Mechanisms of Amphotericin B Pore Formation

Abstract

After more than fifty years since it was first used as an anti fungal drug, Amphotericin B is still the drug of choice for the treatment of systemic fungal infections. Late research about this drug consist essentially in pharmacological tests or in-vivo studies, as well as the development of new derivatives and mechanisms of drug administration. Nevertheless, all this studies are made without having certainty on the mechanism of action at a cellular level, and a detailed description of its structure. Previous results determined the number of molecules involved in the different types of channels, using the equation g=a[AmB]n. These conductances were determined by single channel studies and showed that the most accepted mode of action of the drug, which consists in a barrel-like structure, needs a more complex arrangement to reproduce the experimental results. These results also suggest the existence of a lower conductance AmB channel. Low noise experiments and the development of a new software to analyze the experimental data shows the existence of this lower conductance channel and allows the addition of more experimental data to test the model proposed previously. This results were also used to test new models of AmB channel which require an extra degree of freedom for the molecules involved in the formation of the pore.