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How do ionic channel properties depend on the structure of polyene antibiotic molecules?

K M Kasumov·M P Borisova·L N Ermishkin·V M Potseluyev·A Y Silberstein·V A Vainshtein
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Abstract

A study has been made of the properties of ionic channels formed in phospholipid-cholesterol bilayers by polyene antibiotics of various molecular structures. Properties of channels created by natural antibiotics with different structures of the lactone ring (amphotericin B-nystatin-mycoheptin) as well as by some derivatives of amphotericin B modified with respect to the amino and carboxyl groups are compared. Neutralization of one or both charges of the amphotericin B molecule (both by chemical modification and by pH shift) increases the probability of the channel to be in a nonconducting state. An increase of cholesterol concentration in the membrane produces an opposite effect. It is assumed that the electrostatic interaction of the amino group of an antibiotic molecule with the carboxyl group of an adjacent one stabilized the channel. Conductance and selectivity of an open channel are not influenced by changes in the charged groups. These properties strongly depend on the structure of the polar chain of the lactone ring. For example, the appearance of one more carbonyl group in the mycoheptin molecule results in a sharply decreasing anion permeability of channels. An antibiotic concentration which is necessary to observe single channels depends on the polyene chain structure: this is about 10(-7) M for tetraene nystatin and 2.10(-8) M for heptaene amphotericin B an mycoheptin.

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Amphotericin BAntifungal AgentsCholesterolHydrogen-Ion ConcentrationIon ChannelsMembranes, ArtificialNystatinPhospholipidsPolyenesJournal Article

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K M Kasumov, M P Borisova, L N Ermishkin, V M Potseluyev, A Y Silberstein, V A Vainshtein. 1979-03-08. How do ionic channel properties depend on the structure of polyene antibiotic molecules?. https://doi.org/10.1016/0005-2736(89)90001-1

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PubMed1979

The shape of red blood cells as a function of membrane potential and temperature.

It is well known that a pH shift of the outside medium from 5 to 9 produces a shape transformation of washed human red blood cells from stomatocytes to echinocytes in isotonic salt solutions. In addition, a stomatocytogenic effect is demonstrated here due to solutions of low ionic strength (below 70 mM). An analysis of the true cell state in these situations, proved by measurements of predicted volume changes, indicates a good correlation between transmembrane potential and cell shape. The fact that amphotericin B acts as echinocytogenic agent in low ionic strength medium at pH 7.4 but not at pH 5.1 underlines this explanation. Therefore, a transmembrane potential positive inside produces stomatocytes, slightly negative inside (below--10 mV), normocytes, and strongly negative, echinocytes. The temperature dependence of this process underlines the rigidity-pattern hypothesis of red blood cell shape (Glaser & Leitmannová, 1975, 1977).

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