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D C Tosteson

Publications and source records attributed to D C Tosteson.

At least 55 records · Page 3Linked to original sources
PubMed1984

Electrolyte composition and equilibrium in hemoglobin CC red blood cells.

The red cells of two patients with homozygous hemoglobin C disease (CC) were found to have reduced cation and water content when compared to the red cells of two normal subjects that contained only hemoglobin A (AA). The reduction in cation content was of such a magnitude that the intracellular chloride and hydroxyl (and proton) concentrations were within normal limits despite a measured reduction in the concentration of impermeant negative anions in CC as compared with AA cells of 40 mEq/kg of dry cell solids. The osmotic coefficient of hemoglobin C in CC cells was found to be similar to that observed for hemoglobin A in AA cells. We found no evidence for increased amounts of bound or osmotically abnormal water in CC cells. The reduction in cell cation content in CC cells is mainly due to a reduction in cell K content. The reduced K content is probably related to an increased ouabain- and furosemide-insensitive pathway for K transport in CC cells.

Acid-Base Equilibrium↗
PubMed1982

Effects of the plant alkaloid sanguinarine on cation transport by human red blood cells and lipid bilayer membranes.

The plant alkaloid, sanguinarine, inhibits the ouabain-sensitive K -- Na pump and increases the downhill, ouabain-insensitive movements of K and Na in human red cells. These two effects have different temporal and concentration dependencies and are mediated by two different chemical forms of sanguinarine. The oxidized, charged form (5 X 10(-5) M) promptly inhibits the pump but does not affect leakage of K and Na. The reduced, uncharged form of sanguinarine causes lysis of red cells but does not inhibited the pump. Sanguinarine also increases the conductance of bilayers formed from sheep red cell lipids. The effect is produced by the uncharged but not by the charged form of sanguinarine. Bilayer conductance increases as the fourth power of sanguinarine concentration when the compound is present on both sides of the membrane and as the second power of concentration when present on only one side. Conductance also increase e-fold for each 34 mV increase in the potential difference imposed across the membrane. The results suggest that the uncharged forms of sanguinarine product voltage-dependent channels in bilayers.

Alkaloids↗
PubMed1981

The sting. Melittin forms channels in lipid bilayers.

Melittin, a toxin of bee venom, is a cationic polypeptide composed of 26 amino acids. The six residues of the C-terminal end are polar and 19 of the 20 residues of the N-terminal end are hydrophobic. Exposure of the lecithin bilayer to melittin results in the formation of channels that are more permeable to anions that to cations. Unilateral addition of melittin produces a voltage-dependent increase in membrane conductance when the side where the polypeptide is present in made positive but not when it is made negative. At a fixed voltage, the conductance increases with the fourth power of the melittin concentration in the aqueous phase. At a fixed peptide concentration, the conductance increases approximately e-fold per 6-mV increase in the electrical potential difference across the membrane. These results suggest that four melittin monomers are needed to form a channel and, furthermore, that a minimum of four equivalent electronic charges need to be displaced by the electrical field to explain the voltage dependence of the conductance.

Bee Venoms↗
PubMed1981

Lithium and mania.

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Affective Disorders, Psychotic↗
PubMed1981

Ki+-Nao+ countertransport in erythrocytes of patients with essential hypertension.

1. We describe in this paper a new ouabain-insensitive pathway for Na+ and K+ in human erythrocytes. K+ efflux was measured in cells loaded by the p-chloromercuribenzene-sulphonate (PCMBS) procedure to contain approximately equal amounts of Na+ and K+. K+ efflux was stimulated by external Na+ in the presence of ouabain and frusemide. Na+-stimulated K+ efflux was 0.35 +/- 0.12 (mmol h-1 l-1 of cells) in eight normal subjects and 0.64 +/- 0.13 in 13 patients with essential hypertension. 2. The Na+-stimulated K+ efflux was not observed in cells loaded in the presence of EGTA. This inhibition by EGTA suggests that K+ efflux is dependent on intracellular calcium. The Ki+-Nao+ countertransport of hypertensive patients was also inhibited by EGTA. The elevated K+-Na+ countertransport of hypertensive patients could be due to a higher intracellular Ca2+ content (Ca2i+) or to an increased affinity for Cai2+. The relationship of this pathway to the Gardos effect is not clear since Na+-stimulated K+ efflux occurs without metabolic depletion or inhibition of the Ca2+ pump. As a tentative hypothesis, we relate the Ca2+-dependent downhill movement of K+ and Na+ to the Ca2+-dependent channels described in muscle and nerve, but other hypotheses cannot be excluded at this stage of our research.

Cell Membrane Permeability↗
PubMed1981

Ion transport mediated by the valinomycin analogue cyclo(L-Lac-L-Val-D-Pro-D-Val)3 in lipid bilayer membranes.

Cyclo(L-Lac-L-Val-D-Pro-D-Val)3 (PV-Lac) a structural analogue of the ion-carrier valinomycin, increases the cation permeability of lipid bilayer membranes by forming a 1:1 ion-carrier complex. The selectively sequence for PV-Lac is identical to that of valinomycin; i.e., Rb+ greater than K+ greater than Cs+ greater than or equal to NH+4 greater than Na+ greater than Li+. The steady-state zero-voltage conductance, G(0), is a saturating function of KCl concentration. A similar behavior was found for Rb+, Cs+, and NH+4. However, the ion concentration at which G(0) reaches a plateau strongly depends on membrane composition. The current-voltage curves present saturating characteristics, except at low ion concentrations of Rb+, K+, or Cs+. The ion concentration at which the saturating characteristics appear depends on membrane composition. These and other results presented in this paper agree with a model that assumes complexation between carrier and ion at the membrane-water interface. Current relaxation after voltage-jump studies were also performed for PV-Lac. Both the time constant and the amplitude of the current after a voltage jump strongly depend on ion concentration and membrane composition. These results, together with the stationary conductance data, were used to evaluate the rate constants of the PV-Lac-mediated K+ transport. In glycerolmonooleate they are: association rate constant, 2 x 10(6) M-1 s-1; dissociation rate constant, 4 x 10(5) s-1; translocation rate constant for complex, 5 x 10(4) s-1; and the rate of translocation of the free carrier (ks), 55 s-1. ks is much smaller for PV-Lac than for valinomycin and thus limits the efficiency with which the carrier is able to translocate cations across the membrane.

Biological Transport↗
PubMed1981

Na countertransport and cotransport in human red cells: function, dysfunction, and genes in essential hypertension.

We describe in this paper studies on the modes of operation of ouabain-insensitive sodium transport systems in red cells of normotensive and hypertensive patients. We have extensively investigated the properties of Na countertransport and cotransport in order to clarify whether they are two different proteins or one transport protein with two modes of operation. Several criteria of discrimination between the two pathways are described: They differ in their affinity for Na and Li, sensitivity to several inhibitors, changes in cell volume, and chloride replacement by nitrate. We propose that there are two different transport systems. We have found elevated countertransport in red cells of hypertensive patients in France and in the United States. However, the cotransport system was found elevated in patients in Boston but reduced in patients in Paris. Studies of the modes of operation of the Na-K cotransport system indicate that it can promote K accumulation using an inward sodium gradient. This mode might be more efficient than Na extrusion at the physiological level of Na and K gradients. We interpret our findings of elevated Na-K cotransport in American hypertensive patients as an increased number of transport units functioning as K accumulators. It remains to be determined whether the reduced affinity for internal sodium of the outward cotransport is a defective outward cotransport or else a modulation of this transport system to favor K accumulation.

4-Chloromercuribenzenesulfonate↗
PubMed1980

Cation movements across mouse red blood cells.

This paper describes some features of the Na and K transport systems in red cells obtained from B10.A mice. When mouse erythrocytes were incubated in a plasma-like control medium, the scillaren-sensitive Na efflux was 3.6 +/- 0.4 mmol/l red blood cells per h while the scillaren-sensitive K influx was 3.1 +/- 0.3, values not significantly different from ech other. Scillaren had no significant effect on either Na influx or K efflux. There was a large (approx. 3 mmol/l red blood cells per h) scillaren-sensitive, Na-Na exchange diffusion component present under K-free conditions. When K was present in the incubation medium, this exchange system was suppressed.

Animals↗
PubMed1980

Increased sodium-lithium countertransport in red cells of patients with essential hypertension.

This paper describes experiments showing that one of the pathways of sodium transport across the red-cell membrane, sodium-lithium countertransport, is faster in patients with essential hypertension than in control subjects. This transport system accepts only sodium or lithium and is not inhibited by ouabain. The maximum rate of transport shows inherited differences. The mean maximum rate of sodium-lithium countertransport was found to be 0.55 +/- 0.02 (mean +/- S.E.M.) mmol (liter of red cells X hour)(-1) in a group of 36 patients with essential hypertension and 0.24 +/- 0.02 in 26 control subjects (P less than 0.001). The first-degree relatives of eight patients with essential hypertension and 10 control subjects had mean maximum rates of sodium-lithium countertransport of 0.54 +/- 0.05 and 0.23 +/- 0.02, respectively. Five patients with secondary hypertension had normal mean maximum rates of sodium-lithium countertransport. The relation between heritability of red-cell sodium-lithium countertransport and essential hypertension should be investigated further.

Biological Transport↗
PubMed1980

Cholera toxin interactions with lipid bilayers.

The purpose of the experiments described in this paper was to assess the binding of cholera toxin to bilayers containing its receptor, the monosialoganglioside, GMl. The assay was based on the fact that GMl confers on the bilayer a negative surface charge. The magnitude of this surface charge was estimated by measuring the electrical conductance (G) of the bilayers exposed to nonactin-K+ under conditions where G is directly proportional to the potassium concentration in the aqueous solutions immediatey adjacent to the membrane surface. When bilayers were formed from mixtures of GMl and glycerolmonooleate (GMO), it was found that the molar ratio of the lipids in the bilayer was the same as that in the membrane forming solution. It was further found that cholera toxin or the binding subunit of the toxin (choleragenoid) bind to GMO bilayers containing GMl (but not to GMO bilayers containing phosphatidyl serine or disialoganglioside GDla). The value of the apparent dissociation constant for the binding of choleragen to its receptor was found to be 10(-11) M, comparable to values found in intact cells.

Binding Sites↗
PubMed1979

Learning in medicine.

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Attitude of Health Personnel↗
PubMed1979

Effect of membrane potential and internal pH on active sodium-potassium transport and on ATP content in high-potassium sheep erythrocytes.

Ouabain-sensitive Na+ and K+ fluxes and ATP content were determined in high potassium sheep erythrocytes at different values of membrane potential and internal pH. Membrane potential was adjusted by suspending erythrocytes in media containing different concentrations of MgCl2 and sucrose. Concomitantly either the external pH was changed sufficiently to maintain a constant internal pH or the external pH was kept constant with a resultant change of internal pH. The erythrocytes were preincubated before the flux experiment started in a medium which produced increased ATP content in order to avoid substrate limitation of the pump. It was found that an increased cellular pH reduced the rates of active transport of Na+ and K+ without significantly altering the ratio of pumped Na+/K+. This reduction was not due to limitation in the supply of ATP although ATP content decreased when internal pH increased. Changes of membrane potential in the range between -10 and +60 mV at constant internal pH did not affect the rates of active transport of Na+ or K+.

Adenosine Triphosphate↗
PubMed1978

Some effects of trinitrocresolate and valinomycin on Na and K transport across thin lipid bilayer membranes: a steady-state analysis with simultaneous tracer and electrical measurements.

This paper describes the effect of trinitrocresolate anions (TNC-) on the electrical conductance (Gm), and tracer-measured unidirectional Na and K fluxes (MNa and MK) across bilayers formed from sheep red cell lipids dissolved in decane. In the absence of TNC-, typical low conductances were observed, while the cation fluxes were too low to measure by our techniques (less than 10(-12) moles cm-2 sec-1). In the presence of TNC- (10(-2) M), Gm increased and TNC- was the main charge carrier in the system. The cationic fluxes were also much increased, but the membranes showed no significant selectivity between K and Na. Furthermore, the Na and K fluxes were at least two orders of magnitude larger than the ionic fluxes calculated from Gm. Thus, almost all of the K and Na transport across the membrane in the presence of TNC- is electrically silent and is probably carried out as KTNC and NaTNC ion pairs. In the presence of valinomycin (10(-6) M) and no TNC-, both the ion fluxes and Gm were 10(3) times larger in KCl than in NaCl, thus exhibiting the characteristic high selectivity of valinomycin for K over Na. In the presence of both valinomycin (10(-6) M) and TNC- (10(-2) M), this selectivity disappeared in that both Gm and MNa in the NaCl system were similar to the respective values in the KCl system. Even under these conditions, most of the Na is still transported by a process which does not carry charge. Both Gm and Mx increased alike and monotonically with increasing temperature over the range 7 to 30 degrees C. In the absence of TNC- the enthalpies of activation were invariably higher in KCl than in NaCl. Addition of TNC- produced equal enthalpies of activation for both Na and K containing systems suggesting a common, temperature-dependent, rate-determining step in charge transfer and the electrically silent cation fluxes.

Biological Transport↗