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Biomedical subjects

A K Solomon

Publications and source records attributed to A K Solomon.

At least 91 records · Page 5Linked to original sources

Cation transport in dog red cells.

Studies have been made on the cation transport system of the dog red cell, a system of particular interest because it has been shown that there is a marked dependence of cation fluxes on the cell volume. We have found that a 10% decrease in cell volume causes a large increase in 1 hr uptake of (24)Na as well as a considerable inhibition of (42)K uptake. This effect cannot be produced by a difference in medium osmolality but rather requires the cell volume to change. Dog red cell uptake of (24)Na is not inhibited by iodoacetate. Phloretin inhibits (24)Na uptake and lactate production, and virtually abolishes the volume effect on Na uptake. These several observations may be accounted for in terms of a working hypothesis which presupposes a cation carrier complex which pumps K into and Na out of cells of normal volume. When the cells are shrunken the carrier specificity shifts to an external Na-specific mode and there is a large increase in (24)Na uptake, driven by the inwardly directed Na electrochemical potential gradient.

Animals↗

Hemoglobin charge dependence on hemoglobin concentration in vitro.

Studies have been made of the dependence of the charge of the hemoglobin molecule on hemoglobin concentration in the concentration range between 3 and 11 mmolal. The charge has been determined by measuring the distribution of (42)K between a hemoglobin solution in a cellophane bag and an external solution. The pH was 6.6, the K concentration was 10 mM, and the temperature was 4 degrees C. The charge decreased along a sigmoid curve from a value of +3 in the most dilute solutions to a value of +0.5 in the most concentrated solutions. The results were in excellent agreement with earlier studies of Gary-Bobo and Solomon in which Cl distribution was measured between human red cells and external solutions and thus give added support to the conclusion that the apparent anomalous osmotic behavior of human red cells may be attributed to concentration-dependent changes in the hemoglobin net charge. The present findings also support the view that the water in the red cell is solvent water for K and Cl and differs in no quantitatively important respect from bulk water in free solution.

Journal Article↗

Effect of geometrical and chemical constraints on water flux across artificial membranes.

Studies have been made on the temperature dependence of both the hydraulic conductivity, L(p), and the THO diffusion coefficient, omega, for a series of cellulose acetate membranes (CA) of varying porosity. A similar study was also made of a much less polar cellulose triacetate membrane (CTA). The apparent activation energies, E(a), for diffusion across CA membranes vary with porosity, being 7.8 kcal/mole for the nonporous membrane and 5.5 kcal/mole for the most porous one. E(a) for diffusion across the less polar CTA membrane is smaller than E(a) for the CA membrane of equivalent porosity. Classical viscous flow, in which the hydraulic conductivity is inversely related to bulk water viscosity, has been demonstrated across membranes with very small equivalent pores. Water-membrane interactions, which depend upon both chemical and geometrical factors are of particular importance in diffusion. The implication of these findings for the interpretation of water permeability experiments across biological membranes is discussed.

Acetates↗

Permeability of red cell membranes to small hydrophilic and lipophilic solutes.

The permeability coefficients of a series of amides, ureas, and diols have been measured on red cells of man and dog using the minimum volume method of Sha'afi et al. When the molecules are grouped according to their ether-water partition coefficients, k(ether), the behavior of the hydrophilic molecules, with k(ether) less than water, is different from that of the lipophilic molecules, characterized by k(ether) greater than water. The rate of permeation of the hydrophilic molecules through an aqueous pathway is determined by the molar volume, a parameter in which the geometrical measure of molecular volume is modified by hydrogen-bonding ability. This indicates the importance of chemical interactions within the aqueous path. The permeation of the lipophilic molecules is determined in the first instance by k(ether), taken as a measure of the ease with which the molecule can escape from its aqueous environment. Within the membrane, lipophilic permeability is modified both by steric factors and by the formation of hydrogen bonds with membrane components. These data allow one to infer that lipid-soluble molecules travel through an organized structure within the lipid membrane and come into contact with polar moieties.

Acetamides↗

Tracer determinations of human red cell membrane permeability to small nonelectrolytes.

A flow system has been used to determine the permeability of human red cell membranes to four small nonelectrolytes labeled with (14)C. The permeability coefficients, omega, in units of mol dyne(-1) sec(-1) x 10(15), are: ethylene glycol, 6; urea, 13; formamide, 22; and methanol, 131. The values for urea and formamide are in good agreement with values obtained by Sha'afi, Gary-Bobo, and Solomon by the minimum method. The unusually high value for omega for methanol is ascribed to its solubility in the red cell membrane since its ether: water partition coefficient is 0.14, higher by more than an order of magnitude than the ether: water partition coefficient for water. The other three solutes are hydrophilic and are characterized by values of omega which behave consistently with those of other hydrophilic amides and ureas. The values of omega for the three hydrophilic solutes measured are also consistent with an equivalent pore radius of about 3.5 A in agreement with previous estimates made on the basis of other types of studies.

Amides↗

Transport parameters in a porous cellulose acetate membrane.

The transport parameters of a cellulose acetate membrane prepared from a mixture of cellulose acetate, formamide, and acetone, 25:25:50 by weight, were studied. The membrane consists of a thin, porous layer, the skin, in series with a thick, highly porous layer, the coarse support. In the skin the diffusional permeability coefficient, omega, of a number of small amides and alcohols depends critically upon the partition coefficient, K(s), the size of the molecule, and the apparent hydrogen-bonding ability, N(s), of the solute. These observations are in general agreement with our earlier conclusions on the properties of nonporous membranes. On the other hand, the corrected reflection coefficient, sigma', is not a very sensitive function of either N(s) or K(s) taken separately. The correlation between sigma' and molecular diameter is reasonably good; however, it is much improved when both N(s) and K(s) are taken into consideration. Isotope interaction was also studied in the present preparation and was found to provide only a small (5-8%) contribution to the diffusional permeability coefficient of ethylene glycol. The contribution of solute-water friction was found to be less than 24% of the total solute friction.

Acetates↗

Determination of urea permeability in red cells by minimum method. A test of the phenomenological equations.

A new method has been developed for measuring the permeability coefficient, omega, of small nonelectrolytes. The method depends upon a mathematical analysis of the time course of cell volume changes in the neighborhood of the minimum volume following addition of a permeating solute to an isosmolal buffer. Coefficients determined by the minimum volume method agree with those obtained using radioactive tracers. omega for urea in human red cells was found to decrease as the volume flow, J(v), into the cell increased. Such behavior is entirely unexpected for a single uniform rate-limiting barrier on the basis of the linear phenomenological equations derived from irreversible thermodynamics. However, the present findings are consonant with a complex membrane system consisting of a tight barrier on the outer face of the human red cell membrane and a somewhat less restrictive barrier behind it closer to the inner membrane face. A theoretical analysis of such a series model has been made which makes predictions consistent with the experimental findings.

Cell Membrane Permeability↗

The state of water in human and dog red cell membranes.

The apparent activation energy for the water diffusion permeability coefficient, P(d), across the red cell membrane has been found to be 4.9 +/- 0.3 kcal/mole in the dog and 6.0 +/- 0.2 kcal/mole in the human being over the temperature range, 7 degrees to 37 degrees C. The apparent activation energy for the hydraulic conductivity, L(p), in dog red cells has been found to be 3.7 +/- 0.4 kcal/mole and in human red cells, 3.3 +/- 0.4 kcal/mole over the same temperature range. The product of L(p) and the bulk viscosity of water, eta, was independent of temperature for both dog and man which indicates that the geometry of the red cell membrane is not temperature-sensitive over our experimental temperature range in either species. In the case of the dog, the apparent activation energy for diffusion is the same as that for self-diffusion of water, 4.6-4.8 kcal/mole, which indicates that the process of water diffusion across the dog red cell membrane is the same as that in free solution. The slightly, but significantly, higher activation energy for water diffusion in human red cells is consonant with water-membrane interaction in the narrower equivalent pores characteristic of these cells. The observation that the apparent activation energy for hydraulic conductivity is less than that for water diffusion across the red cell membrane is characteristic of viscous flow and suggests that the flow of water across the membranes of these red cells under an osmotic pressure gradient is a viscous process.

Animals↗

Cellular inhomogeneity in dog red cells as revealed by sodium flux.

Unidirectional (24)Na fluxes across the dog red blood cell membrane were measured. The kinetics were incompatible with a single time constant but could be accounted for in terms of a two-series compartment cell model, with approximately 1% of cell Na in the outer compartment. Dog red blood cells are known to be inhomogeneous in their Na and K permeabilities. Theoretical analysis showed that such cellular inhomogeneity in the Na permeability coefficient might in principle account for the flux data. In order to evaluate the inhomogeneity effect, a technique based on the differential response of cells suspended in isosmolar high K buffers was devised to measure the variations in Na permeability in the cell population. A variation in the Na permeability coefficient of approximately 30% was found. This inhomogeneity is insufficient to account for the flux data.

Animals↗

Role of hydrogen-bonding in nonelectrolyte diffusion through dense artificial membranes.

The diffusion of two series of alcohols and amides through complex cellulose acetate membranes was studied. The thin dense part of these membranes behaves as a nonporous layer of low water content. In this layer, called the skin, the solute diffusion coefficients, omega, depend upon size, steric configuration, and the partition coefficient, K(8), between membrane and bathing solution. From the experimental values of omega and K(8), the over-all friction, f, experienced by the solutes in the membrane was computed. It was found that f depends upon the chemical nature of the solute and is related to hydrogen-bonding ability. In the coarse, porous layer of the cellulose acetate membrane, diffusion occurs mainly through aqueous channels. In this instance also the hydrogen-bonding ability of the solute seems to exercise a smaller but significant influence.

Acetates↗

Osmotic volume flow in the proximal tubule of Necturus kidney.

Volume changes due to osmotic flow in the distal portion of proximal tubules of Necturi were measured by the split oil drop technique. In agreement with previous findings no volume flow was induced by NaCl concentrations close to 60 mM. The tubule wall was found to be permeable to plasma electrolytes, which have an apparent reflection coefficient of 0.69. The mean apparent hydraulic conductivity was 0.33 x 10(-11) cm(3)/dyne sec, comparable with other epithelia. A number of lipid-insoluble nonelectrolytes of widely varying molecular size had apparent reflection coefficients of about 0.5. In view of the insensitivity to molecular size it seems likely that apparent reflection coefficients determined from tubular volume changes depend primarily on the porosity of the intercellular barrier closest to the lumen and give little information about the subsequent fate of the test substances.

Animals↗

Properties of hemoglobin solutions in red cells.

The present studies are concerned with a detailed examination of the apparent anomalous osmotic behavior of human red cells. Red cell water has been shown to behave simultaneously as solvent water for nonelectrolytes and nonsolvent water, in part, for electrolytes. The nonsolvent properties are based upon assumptions inherent in the conventional van't Hoff equation. However, calculations according to the van't Hoff equation give osmotic volumes considerably in excess of total cell water when the pH is lowered beyond the isoelectric point for hemoglobin; hence the van't Hoff equation is inapplicable for the measurement of the solvent properties of the red cell. Furthermore, in vitro measurements of osmotic and other properties of 3.7 millimolal solutions of hemoglobin have failed to reveal the presence of any salt exclusion. A new hypothesis has been developed from thermodynamic principles alone, which predicts that, at constant pH, the net charge on the hemoglobin molecule decreases with increased hemoglobin concentration. The existence of such cooperative interaction may be inferred from the effect of pH on the changes in hemoglobin net charge as the spacing between the molecules decreases. The resultant movement of counterions across the cell membrane causes the apparent anomalous osmotic behavior. Quantitative agreement has been found between the anion shift predicted by the equation and that observed in response to osmotic gradients. The proposed mechanism appears to be operative in a variety of tissues and could provide an electrical transducer for osmotic signals.

1-Propanol↗

Effect of osmolality on the hydraulic permeability coefficient of red cells.

The osmotic water permeability coefficient, L(p), for human and dog red cells has been measured as a function of medium osmolality, and found to depend on the osmolality of the bathing medium. In the case of human red cells L(p) falls from 1.87 x 10(-11) cm(3)/dyne sec at 199 mOSM to 0.76 x 10(-11) cm(3)/dyne sec at 516 mOSM. A similar decrease was observed for dog red cells. Moreover, L(p) was independent of the direction of water movement and the nature of the solute used to provide the osmotic pressure gradient; it depended only on the final osmolality of the medium. Furthermore, L(p) was not affected by pH in the range of 6 to 8 nor by the presence of drugs such as valinomycin (1 x 10(-6)M) and tetrodotoxin (3.2 x 10(-6)M). The instantaneous nature of the response to changes in external osmolality suggests that the hydraulic conductivity of the membrane is controlled by a thin layer at the outer face of the membrane.

Animals↗