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D C Tosteson

Publications and source records attributed to D C Tosteson.

At least 91 records · Page 5Linked to original sources
PubMed1974

Effect of peptide PV on the ionic permeability of lipid bilayer membranes.

THIS PAPER REPORTS THE EFFECTS OF PEPTIDE PV (PRIMARY STRUCTURE: cyclo-(D-val-L-pro-L-val-D-pro)(delta)) on the electrical properties of sheep red cell lipid bilayers. The membrane conductance (G(m)) induced by PV in either Na(+) or K(+) medium is proportional to the concentration of PV in the aqueous phase. The PV concentration required to produce a comparable increase in G(m) in K(+) medium is about 10(4) times greater than for its analogue, valinomycin (val). Although the selectivity sequence for PV and val is similar, K(+) greater, similar Rb(+) > Cs(+) > NH(4) (+) > TI(+) > Na(+) > Li(+); the ratio of GGm in K(+) to that in Na(+) is about 10 for PV compared to > 10(3) for val. When equal concentrations of PV are added to both sides of a bilayer, the membrane current approaches a maximum value independent of voltage when the membrane potential exceeds 100 mV. When PV is added to only one side of a bilayer separating identical salt solutions of either Na(+) or K(+) salts, rectification occurs such that the positive current flows more easily away rather than toward the side containing the carrier. Under these conditions, a large, stable, zero-current potential (VVm) is also observed, with the side containing PV being negative. The magnitude of this VVm is about 90 mV and relatively independent of PV concentration when the latter is larger than 2 Times; 10(-5) M. From a model which assumes that V(m) equals the equilibrium potential for the PV-cation complexes (MS(+)) and that the reaction between PV and cations is at equilibrium on the two membrane surfaces, we compute the permeability of the membrane to free PV to be about 10(-5) cm s(-1), which is about 10(-7) times the permeability of similar membranes to free val. This interpretation is supported by the fact that the observed values of V(m) are in agreement with the calculated equilibrium potential for MS(+) over a wide range of ratios of concentrations of total PV in the two bathing solutions, if the unstirred layers are taken into account in computing the MS(+) concentrations at the membrane surfaces.

Animals↗
PubMed1973

Diffusion of weak acids across lipid bilayer membranes: effects of chemical reactions in the unstirred layers.

Chemical reactions in the aqueous unstirred layers of solution adjacent to a membrane can have dramatic effects on the diffusion of solutes across that membrane. This is demonstrated by the diffusion of labeled salicylate and salicylic acid across a phospholipid bilayer membrane. Two types of chemical reactions are considered. The first is an isotopic exchange reaction between the ionic and nonionic forms of a weak acid, HA + *A(-) [unknown] H*A + A(-). This reaction provides a way of estimating the true membrane permeability to a highly permeant weak acid and also a way of estimating the thickness of the unstirred layers. The second chemical reaction, the dissociation of a weak acid, HA [unknown] H(+) + A(-), can be used to show how the presence or absence of buffers in the unstirred layers controls the net transport of permeant weak acids across a membrane. In principle, the addition of appropriate "antacid" buffers to salicylates can increase their rate of absorption from the stomach.

Carbon Radioisotopes↗
PubMed1973

Characteristics of chloride transport in human red blood cells.

The efflux of chloride-36 from human erythrocytes under steady-state conditions is a saturable process that is competitively inhibited by bicarbonate and noncompetitively inhibited by acetate. This chloride self-exchange flux is reversibly dependent on the pH of the medium between 5.7 and 9.6 with a maximum flux at pH 7.8. The increase in chloride flux between pH 5.7 and 7.8 is inexplicable by the fixed charge hypothesis. The interpretations are made that chloride transport in human erythrocytes is carrier mediated, that bicarbonate utilizes the same transport mechanism, and that the mechanism can be titrated with hydrogen ions into less functional forms for chloride transport.

Acetates↗
PubMed1972

The permeability of thin lipid membranes to bromide and bromine.

Thin lipid (optically black) membranes were made from sheep red cell lipids dissolved in n-decane. The flux of Br across these membranes was measured by the use of tracer (82)Br. The unidirectional flux of Br (in 50-100 mM NaBr) was 1-3 x 10(-12) mole/cm(2)sec. This flux is more than 1000 times the flux predicted from the membrane electrical resistance (>10(8) ohm-cm(2)) and the transference number for Br(-) (0.2-0.3), which was estimated from measurements of the zero current potential difference. The Br flux was not affected by changes in the potential difference imposed across the membrane (+/-60 mv) or by the ionic strength of the bathing solutions. However, the addition of a reducing agent, sodium thiosulfate (10(-3)M), to the NaBr solution bathing the membrane caused a 90% reduction in the Br flux. The inhibiting effect of S(2)O(3) (=) suggests that the Br flux is due chiefly to traces of Br(2) in NaBr solutions. As expected, the addition of Br(2) to the NaBr solutions greatly stimulated the Br flux. However, at constant Br(2) concentration, the Br flux was also stimulated by increasing the Br(-) concentration, in spite of the fact that the membrane was virtually impermeable to Br(-). Finally, the Br flux appeared to saturate at high Br(2) concentrations, and the saturation value was roughly proportional to the Br(-) concentration. These results can be explained by a model which assumes that Br crosses the membrane only as Br(2) but that rapid equilibration of Br between Br(2) and Br(-) occurs in the unstirred layers of aqueous solution bathing the two sides of the membrane. A consequence of the model is that Br(-) "facilitates" the diffusion of Br across the unstirred layers.

Animals↗
PubMed1971

The effect of valinomycin on the electrical properties of solutions of red cell lipids in n-decane.

This paper reports the electrical properties of thick lipid membranes in the absence and presence of valinomycin. The thick lipid membranes were formed by placing a solution of sheep red cell lipids in decane between two cellophane partitions which formed the interfaces between the membrane and the two aqueous bathing solutions. The DC electrical resistance of these structures was found to be directly proportional to the reciprocal of the concentration of lipids in the decane (C(L)). The limiting resistance, as (C(L) (-1)) approached zero, was 3 x 10(8) ohm-cm(2). Resistance was also found to be linearly related to membrane thickness. The limiting resistance at zero thickness was again 1-3 x 10(8) ohm-cm(2). These data are interpreted to indicate that the DC resistance of thick lipid membranes comprises two surface resistances (R(S)) at each interface with the aqueous bathing solutions, and a bulk resistance (R(B)) of the lipid-decane solution, arranged in series. Measurements of the effect of variations of area on resistance were consistent with this interpretation. Valinomycin reduced R(S) but had no effect on R(B). Under certain conditions, thick lipid membranes containing valinomycin behaved like highly selective K(+) electrodes.

Animals↗
PubMed1971

The effect of 2,4,6-trinitro-m-cresol on cation and anion transport in sheep red blood cells.

2,4,6-Trinitro-3-methyl-phenol (trinitrocresol, H(+)TNC(-)) was found to inhibit anion and stimulate cation movements across the membranes of both high potassium (HK) and low potassium (LK) sheep red blood cells. The concentration of TNC(-) required to inhibit SO(4) (-) and Cl(-) efflux (10(-5)-10(-3)M) was less than that required to increase Na(+) and K(+) leakage (10(-3)-10(-2)M). Both the inhibition of anion and stimulation of cation permeation were reversed if TNC(-) was washed from the red cells. The cation leak caused by TNC(-) was much greater at 0 degrees and 37 degrees C than at room temperature (23 degrees C). In sheep red cells, TNC(-) was found to be about 20 times more effective than salicylate and about 40 times more effective than thiocyanate in increasing cation leak. TNC(-) also inhibited the ouabain-sensitive potassium influx.

Animals↗
PubMed1971

Active sodium and potassium transport in high potassium and low potassium sheep red cells.

The kinetic characteristics of the ouabain-sensitive (Na + K) transport system (pump) of high potassium (HK) and low potassium (LK) sheep red cells have been investigated. In sodium medium, the curve relating pump rate to external K is sigmoid with half maximal stimulation (K(1/2)) occurring at 3 mM for both cell types, the maximum pump rate in HK cells being about four times that in LK cells. In sodium-free media, both HK and LK pumps are adequately described by the Michaelis-Menten equation, but the K(1/2) for HK cells is 0.6 +/- 0.1 mM K, while that for LK is 0.2 +/- 0.05 mM K. When the internal Na and K content of the cells was varied by the PCMBS method, it was found that the pump rate of HK cells showed a gradual increase from zero at very low internal Na to a maximum when internal K was reduced to nearly zero (100% Na). In LK cells, on the other hand, no pump activity was detected if Na constituted less than 70% of the total (Na + K) in the cell. Increasing Na from 70 to nearly 100% of the internal cation composition, however, resulted in an exponential increase in pump rate in these cells to about (1/6) the maximum rate observed in HK cells. While changes in internal composition altered the pump rate at saturating concentrations of external K, it had no effect on the apparent affinity of the pumps for external K. These results lead us to conclude that the individual pump sites in the HK and LK sheep red cell membranes must be different. Moreover, we believe that these data contribute significantly to defining the types of mechanism which can account for the kinetic characteristics of (Na + K) transport in sheep red cells and perhaps in other systems.

Animals↗
PubMed1970

Ionic peremability of thin lipid membranes. Effects of n-alkyl alcohols, polyvalent cations, and a secondary amine.

Ultrathin (black) lipid membranes were made from sheep red cell lipids dissolved in n-decane. The presence of aliphatic alcohols in the aqueous solutions bathing these membranes produced reversible changes in the ionic permeability, but not the osomotic permeability. Heptanol (8 mM), for example, caused the membrane resistance (R(m)) to decrease from >10(8) to about 10(5) ohm-cm(2) and caused a marked increase in the permeability to cations, especially potassium. In terms of ionic transference numbers, deduced from measurements of the membrane potential at zero current, T(cat)/T(Cl) increased from about 6 to 21 and T(K)/T(Na) increased from about 3 to 21. The addition of long-chain (C(8)ndash;C(10)) alcohols to the lipid solutions from which membranes were made produced similar effects on the ionic permeability. A plot of log R(m) vs. log alcohol concentration was linear over the range of maximum change in R(m), and the slope was -3 to -5 for C(2) through C(7) alcohols, suggesting that a complex of several alcohol molecules is responsible for the increase in ionic permeability. Membrane permselectivity changed from cationic to anionic when thorium or ferric iron (10(-4)M) was present in the aqueous phase or when a secondary amine (Amberlite LA-2) was added to the lipid solutions from which membranes were made. When membranes containing the secondary amine were exposed to heptanol, R(m) became very low (10(3)-10(4) ohm-cm(2)) and the membranes became perfectly anion-selective, developing chloride diffusion potentials up to 150 mv.

Alcohols↗
PubMed1969

Inhibition of adenosine triphosphatase in sheep red cell membranes by oxidized glutathione.

This paper reports inhibition of Na(+) + K(+)-stimulated, ouabain-inhibited adenosine triphosphatase (S-ATPase) in sheep red cell membranes by oxidized glutathione (GSSG). The results are consistent with the hypothesis that this inhibition depends upon the formation of a mixed disulfide between glutathione and -SH group(s) in the enzyme protein. Thus, inhibition of S-ATPase by GSSG proceeds more rapidly at alkaline than at neutral pH and is reversed by the addition of an excess of a compound containing reduced -SH groups (e.g. dithiothreitol). ATP protects S-ATPase against inhibition by GSSG and this protection depends on both the monovalent and divalent cation composition of the medium. Protection by ATP is more complete in the presence of K(+) than in the presence of Na(+).

Adenosine Triphosphatases↗