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Biomedical subjects

A Cass

Publications and source records attributed to A Cass.

31 records · Page 2Linked to original sources

The ion permeability induced in thin lipid membranes by the polyene antibiotics nystatin and amphotericin B.

Characteristics of nystatin and amphotericin B action on thin (<100 A) lipid membranes are: (a) micromolar amounts increase membrane conductance from 10(-8) to over 10(-2) Omega(-1) cm(-2); (b) such membranes are (non-ideally) anion selective and discriminate among anions on the basis of size; (c) membrane sterol is required for action; (d) antibiotic presence on both sides of membrane strongly favors action; (e) conductance is proportional to a large power of antibiotic concentration; (f) conductance decreases approximately 10(4) times for a 10 degrees C temperature rise; (g) kinetics of antibiotic action are also very temperature sensitive; (h) ion selectivity is pH independent between 3 and 10, but (i) activity is reversibly lost at high pH; (j) methyl ester derivatives are fully active; N-acetyl and N-succinyl derivatives are inactive; (k) current-voltage characteristic is nonlinear when membrane separates nonidentical salt solutions. These characteristics are contrasted with those of valinomycin. Observations (a)-(g) suggest that aggregates of polyene and sterol from opposite sides of the membrane interact to create aqueous pores; these pores are not static, but break up (melt) and reform continuously. Mechanism of anion selectivity is obscure. Observations (h)-(j) suggest-NH(3) (+) is important for activity; it is probably not responsible for selectivity, particularly since four polyene antibiotics, each containing two-NH(3) (+) groups, induce ideal cation selectivity. Possibly the many hydroxyl groups in nystatin and amphotericin B are responsible for anion selectivity. The effects of polyene antibiotics on thin lipid membranes are consistent with their action on biological membranes.

Amphotericin B↗

Water permeability of thin lipid membranes.

The osmotic permeability coefficient, P(f), and the tagged water permeability coefficient, P(d), were determined for thin (<100 A) lipid membranes formed from ox brain lipids plus DL-alpha-tocopherol; their value of approximately 1 x 10(-3) cm/sec is within the range reported for plasma membranes. It was established that P(f) = P(d). Other reports that P(f) > P(d) can be attributed to the presence of unstirred layers in the experimental determination of P(d). Thus, there is no evidence for the existence of aqueous pores in these thin phospholipid membranes. The adsorption onto the membrane of a protein that lowers its electrical resistance by a factor of 10(3) was found not to affect its water permeability; however, glucose and sucrose were found to interact with the membrane to modify P(f). Possible mechanisms of water transport across these films are discussed, together with the implications of data obtained on these structures for plasma membranes.

Adsorption↗