The Effects of Sodium and Potassium on Ouabain Binding by Human Erythrocytes

Gardner, Jerry D.; Conlon, Thomas P.

doi:10.1085/jgp.60.5.609

Cited by 89 publications

(80 citation statements)

References 10 publications

(16 reference statements)

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“…It is known that these steroids act on the outside of the membrane (Hoffman, 1966;Perrone and Blostein, 1973), and that the ionic composition of the external medium affects the rates at which the binding of the steroid and the inhibition of the pump occur (Hoffman, 1966;Beaug~ and Adragna, 1971;Gardner and Conlon, 1972;Sachs, 1974;Gardner and Frantz, 1974). One experimental approach to this problem has been to study the effects of monovalent cations on the steroid binding in comparison with the effects of these same ions on the pump rate.…”

mentioning

confidence: 99%

Interaction of external alkali metal ions with the Na-K pump of human erythrocytes: a comparison of their effects on activation of the pump and on the rate of ouabain binding.

Hobbs¹,

Dunham²

1978

The Journal of General Physiology

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A B ST R A C T The effects of external alkali metal ions on the rate of ouabain binding and on the rate of the Na-K pump were examined in human red blood cells. In Na-containing solutions, K, Cs, and Li decreased the rate of ouabain binding. For K and Cs, the kinetics of this effect were similar to those for their activation of the pump. In Na-free (choline-substituted) solutions the rate of ouabain binding was decreased by K whereas it was promoted by Cs and Li. External Na increased the rate of ouabain binding whether or not external K was present, and the kinetics of this effect were not the same as tfiose for inhibition of the pump by Na. These findings are interpreted to mean that not only do the cations affect ouabain binding at the external loading sites on the pump from which ions are translocated inward, but that there are additional sites on the external aspect of the pump at which cations can promote ouabain binding, and that these sites can be occupied by Li, Na, and Cs. It is postulated that these latter sites are those from which Na is discharged after outward translocation by the pump.The inhibitory action of cardioactive steroids on the Na-K pump in human erythrocytes has been a subject of study by numerous laboratories in the hopes of acquiring a better understanding of the mechanism of the pump's action (

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mentioning

confidence: 99%

Interaction of external alkali metal ions with the Na-K pump of human erythrocytes: a comparison of their effects on activation of the pump and on the rate of ouabain binding.

Hobbs¹,

Dunham²

1978

The Journal of General Physiology

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“…In intact cells a reciprocal relationship between the binding of ouabain to erythrocytes and the concentration of potassium has been demonstrated (Gardner & Conlon, 1972); a similar relationship between the cellular binding of ouabain and potassium has been demonstrated in myocardial cells (Baker & Willis, 1972;McCall, 1979).…”

Section: Introductionmentioning

confidence: 76%

Time Course of Ouabain Uptake in Isolated Myocardial Cells: Dependence on Extracellular Potassium and Calcium Concentration

Meldgaard

Steiness

Waldorff

1981

British J Pharmacology

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Spontaneously beating myocardial cells isolated from newborn rats have been used to evaluate the time course of cellular ouabain uptake. The rate of cellular uptake and the amount of ouabain bound at equilibrium were computed by fitting the experimental data to the conventional exponential equation for receptor binding of drugs. At normal extracellular potassium and calcium concentrations a biexponential equation was the best fit to the experimental data, indicating two receptor sites of ouabain with different rates of uptake. Increasing extracellular potassium or calcium concentrations decreased the amounts of ouabain bound at equilibrium. 5 High and low extracellular concentrations of potassium or calcium decreased the rate of ouabain uptake. 6 It is well known that ouabain changes ionic fluxes. Changes in the extracellular potassium and calcium concentrations also influence the amount of ouabain taken up by myocardial cells, as demonstrated in the present study.

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“…In these studies it was shown that K+ inhibited the binding of cardiac glycosides in various membrane preparations exhibiting Na+, K+ ATPase activity. The relationship between ouabain receptor affinity and K+ was found to be hyperbolic by Gardner & Conlon (1972) (Figure 4). Moreover, the antagonistic effect ofK + on glycoside binding was dissociated from its effect on the inotropic actions, even though it was shown (Ebner, 1984) (Figure 8).…”

Section: Discussionmentioning

confidence: 98%

“…In various preparations the binding of cardiac glycosides was found to be proportional to the Na+ concentration (Baker & Willis, 1972;Gardner & Conlon, 1972;Lindenmayer et al, 1973;Erdmann & Schoner, 1973;Inagaki etal., 1974;Hobbs & Dunham, 1978;Furukawa et al, 1980). However, the reduction of ouabain receptor affinity cannot be the sole mechanism by which Na+ withdrawal reduces the inotropic effect of cardiac glycosides.…”

Section: Discussionmentioning

confidence: 99%

“…Increases in K+ concentration inhibit the binding of cardiac glycosides (e.g., Gardner & Conlon, 1972), stimulate the Na' pump (for review see Glitsch, 1979), reduce Na' influx (Ellis, 1977;Eisner et al, 1981), and possibly alter electrogenic Na'-Ca2+ exchange (Reeves & Sutko, 1980;Mullins, 1981). Thus, changes in K+ may also alter the positive inotropic effect of cardiac glycosides.…”

Section: Introductionmentioning

confidence: 99%

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Potassium changes the relationship between receptor occupancy and the inotropic effect of cardiac glycosides in guinea‐pig myocardium

Bachmaier¹,

Ebner²,

Reiter³

1985

British J Pharmacology

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I K+ (2.4-15.6mmoll-') antagonized the positive inotropic effect of dihydro-ouabain. The concentration-effect curves became steeper with the shift to higher concentrations of the glycoside. At 1.2 mmol 1-Ca2+, an increase in K+ from 2.4 to 12 mmol 1-P' required tenfold higher concentrations of dihydro-ouabain to produce equal inotropic effects. This factor was reduced to four at 3.2 mmol I-, Ca2+ . The same change in K+ concentration, at 1.2 mmol 1-' Ca2+, diminished the inotropic effect of ouabain on rested-state contractions by a factor of six. 2 The positive inotropic effect of Ca2+ was also antagonized by K+ (1.2-12 mmol 1-'). Reduction of Na+ from 140 to 70 mmol 1-' abolished the antagonistic action of K+ (1.2-8.0 mmol 1-'). Moreover the inotropic effect of Ca2" was enhanced.3 Reduction of Na+, from 140 to 70 mmol -', antagonized the positive inotropic effect of dihydroouabain more at low (2.4 mmol l') than at high (8.0 mmol I') K+. Accordingly, the extent of the dihydro-ouabain-K+ antagonism was reduced. 4 When the K+ concentration was increased from 2.4 to 12mmoll-', [3H]-ouabain binding was reduced by a factor of three. This is less than the reduction in the inotropic effectiveness of ouabain or dihydro-ouabain. 5 Reduction of stimulation frequency from 1 to 0.1215 Hz did not significantly alter the antagonistic effect of K+. Diminution of Vmax of the action potential was observed only at K+ concentrations greater than 5.9 mmol 1-, whereas the resting membrane potential was continuously depolarized over the entire range of K+ concentrations. 6 The results support the view that the reduction in receptor affinity cannot be the sole cause of the antagonism between the glycoside and K+. Impairment of passive Na+ influx during diastole, due to the K+-dependent depolarization of the resting membrane potential, contributed to about one half of the glycoside-K+ antagonism.

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The Effects of Sodium and Potassium on Ouabain Binding by Human Erythrocytes

Cited by 89 publications

References 10 publications

Interaction of external alkali metal ions with the Na-K pump of human erythrocytes: a comparison of their effects on activation of the pump and on the rate of ouabain binding.

Interaction of external alkali metal ions with the Na-K pump of human erythrocytes: a comparison of their effects on activation of the pump and on the rate of ouabain binding.

Time Course of Ouabain Uptake in Isolated Myocardial Cells: Dependence on Extracellular Potassium and Calcium Concentration

Potassium changes the relationship between receptor occupancy and the inotropic effect of cardiac glycosides in guinea‐pig myocardium

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