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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    The journal of membrane biology 1 (1969), S. 346-382 
    ISSN: 1432-1424
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary This paper, the last in a series of three, characterizes the electrical properties of phospholipid bilayer membranes exposed to aqueous solutions containing nonactin, monactin, dinactin, and trinactin and Li+, Na+, K+, Rb+, Cs+, and NH 4 + ions. Not only are both the membrane resistance at zero current and the membrane potential at zero current found to depend on the aqueous concentrations of antibiotic and ions in the manner expected from the theory of the first paper, but also these measurements are demonstrated to be related to each other in the manner required by this theory for “neutral carriers”. To verify that these antibiotics indeed are free to move as carriers of cations, cholesterol was added to the lipid to increase the “viscosity” of the interior of the membrane. Cholesterol decreased by several orders of magnitude the ability of the macrotetralide antibiotics to lower the membrane resistance; nevertheless, the permeability ratios and conductance ratios remained exactly the same as in cholesterolfree membranes. These findings are expected for the “carrier” mechanism postulated in the first paper and serve to verify it. Lastly, the observed effects of nonactin, monactin, dinactin, and trinactin on bilayers are compared with those predicted in the preceding paper from the salt-extraction equilibrium constants measured there; and a close agreement is found. These results show that the theory of the first paper satisfactorily predicts the effects of the macrotetralide actin antibiotics on the electrical properties of phospholipid bilayer membranes, using only the thermodynamic constants measured in the second paper. It therefore seems reasonable to conclude that these antibiotics produce their characteristic effects on membranes by solubilizing cations therein as mobile positively charged complexes.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1424
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary To develop a quantitiative theoretical treatment for the effects of neutral macrocyclic antibiotics on the electrical properties of phospholipid bilayer membranes, this paper proceeds from the known ability of such molecules to form stoichiometric, lipid-soluble complexes with cations and deduces the electrical properties that a simple organic solvent phase would have if it were made into a membrane of the thinness of the phospholipid bilayer. In effect, we postulate that the essential barrier to ion movement across a bilayer membrane is its liquid-like hydrocarbon interior and that the neutral macrocyclic antibiotics bind monovalent cations and solubilize them in the membrane as mobile positively charged complexes. Using the Poisson-Boltzmann equation to describe the equilibrium profile of the electrical potential, it is shown that an excess of the positive complexes over all the other ions is expected in the membrane as a net space charge for appropriate conditions of membrane thickness and values of the partition coefficients of the various ionic species and without requiring the presence of fixed charges. Describing the fluxes of these complexes by the Nernst-Planck equation and neglecting the contribution to the electric current of uncomplexed ions, theoretical expressions are derived for the membrane potential in ionic mixtures, as well as for the limiting value of the membrane conductance at zero current when the membrane is interposed between identical solutions. The expressions are given in terms of the ionic activities and antibiotic concentrations in the aqueous solutions so as to be accessible to direct experimental test. Under suitable experimental conditions, the membrane potential is described by an equation recognizible as the Goldman-Hodgkin-Katz equation, in which the permeability ratios are combinations of parameters predicted from the present theory to be independently determinable from the ratio of membrane conductances in single salt solutions. Since this identity between permeability and conductance ratios is expected also for systems obeying the “Independence Principle” of Hodgkin and Huxley, the applicability of this principle to membranes exposed to antibiotics is discussed, and it is shown that this principle is compatible with the permeation mechanism proposed here.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    The journal of membrane biology 1 (1969), S. 294-345 
    ISSN: 1432-1424
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary In order to clarify the mechanism by which neutral molecules such as the macrotetralide actin antibiotics make phospholipid bilayer membranes selectively permeable to cations, we have studied, both theoretically and experimentally, the extraction by these antibiotics of cations from aqueous solutions into organic solvents. The experiments involve merely shaking an organic solvent phase containing the antibiotic with aqueous solutions containing various cationic salts of a lipid-soluble colored anion. The intensity of color of the organic phase is then measured spectrophotometrically to indicate how much salt has been extracted. From such measurements of the equilibrium extraction of picrate and dinitrophenolate salts of Li, Na, K, Rb, Cs, and NH4 into n-hexane, dichloromethane, and hexane-dichloromethane mixtures, we have verified that the chemical reactions are as simple as previously postulated, at least for nonactin, monactin, dinactin, and trinactin. The equilibrium constant for the extraction of each cation by a given macrotetralide actin antibiotic was also found to be measurable with sufficient precision for meaningful differences among the members of this series of antibiotics to be detected. It is noteworthy that the ratios of selectivities among the various cations were discovered to be characteristic of a given antibiotic and to be completely independent of the solvent used. This finding and others reported here indicate that the size and shape of the complex formed between the macrotetralide and a given cation is the same, regardless of the species of cation bound. For such “isosteric” complexes, notable simplifications of the theory become possible which enable us to predict not only the electrical properties of a membrane made of the same solvent and having the thinness of the phospholipid bilayer but also, and more importantly, the electrical properties of the phospholipid bilayer membrane itself. These predictions will be compared with experimental data for phospholipid bilayer membranes in the accompanying paper.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    The journal of membrane biology 9 (1972), S. 3-36 
    ISSN: 1432-1424
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The cyclic polyether XXXII, a neutral, lipid soluble molecule, produces large increases in the conductance of bilayer membranes formed from a variety of lipids. The conductance increases linearly with the concentration of alkali metal cation but with the square, and at higher concentrations the cube, of the polyether concentration. This implies that two or three polyether molecules combine with a single cation to carry it across the membrane. In the presence of XXXII the bilayer is permeable solely to cations and the membrane potential is described by an equation of the Goldman-Hodgkin-Katz type. The permeability ratios determined from potential measurements are independent of salt concentration, decrease in the sequence Cs〉Rb〉K〉NH4〉Na〉Li(1.0,0.25, 0.15, 0.075, 0.007, 0.0013) and are equal to the conductance ratios at low (e.g. 10−3 m) salt concentration. At higher salt concentrations, the permeability and conductance ratios are not equal and maxima in the conductancevs. salt concentration curves are observed. Both these phenomena are postulated to be caused by the formation of relatively impermeant 1ν1 polyether cation complexes in the aqueous phase. The 1ν1 aqueous association constants deduced from bilayer measurements decrease in the sequence K〉Rb〉Na〉NH4〉Cs〉Li (120, 34, 26, 19, 12, 4 liters per mole) and agree quantitatively with the literature values for the more water soluble polyether XXXI, which lacks only thet-butyl groups of XXXII.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1424
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The manner in which the molecular structure of the carrier and the lipid composition of the membrane modulate the membrane selectivity among monovalent cations has been investigated for nonactin, trinactin, and tetranactin, which differ only in their degrees of methylation, and for membranes made of two lipids, phosphatidyl ethanolamine and glyceryl dioleate, in which “equilibrium” and “kinetic” aspects of permeation, respectively, are emphasized. Bilayer permeability ratios for Li, Na, K, Rb, Cs, Tl, and NH4 have been characterized and resolved into “equilibrium” and “kinetic” components using a model for carrier-mediated membrane transport which includes both a trapezoidal energy barrier for translocation of the complex across the membrane interior and a potential-dependence of the loading and unloading of ions at the membrane-solution interfaces. The bilayer permeability properties due to tetranactin have been characterized in each of these lipids and found not only to be regular but to be systematically related to those of the less methylated homologues, trinactin and nonactin. This analysis has led to the following conclusions: (1) The change in lipid composition alters the relative contributions of “kinetic”vs. “equilibrium” components to the observed carrier-mediated selectivity. (2) Increased methylation of the carrier increases the contribution of the “kinetic” component to the selectivity relative to that of the “equilibrium” component and additionally alters the “equilibrium” component sufficiently that an inversion in Cs−Na selectivity occurs between trinactin and tetranactin. (3) For all ions and carriers examined, the “reaction plane” for ion-carrier complexation and the width for the “diffusion barrier” can be represented by the same two parameters, independent of the ion or carrier, so that in all cases the complexation reaction senses 10% of the applied potential and the plateau of the “diffusion barrier” extends across 70% of the membrane interior.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Inorganic Biochemistry 43 (1991), S. 397 
    ISSN: 0162-0134
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Bulletin of Mathematical Biology 46 (1984), S. 41-80 
    ISSN: 0092-8240
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Mathematics
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Bulletin of Mathematical Biology 46 (1984), S. 41-80 
    ISSN: 0092-8240
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Mathematics
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 16 (1987), S. 205-226 
    ISSN: 0084-6589
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0301-4622
    Keywords: Eu3^3^+ luminescence ; Icosahedral virus ; Ion selectivity ; Satellite tobacco necrosis virus
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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