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.

Hobbs, A S; Dunham, Philip B.

doi:10.1085/jgp.72.3.381

Cited by 18 publications

(11 citation statements)

References 32 publications

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“…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%

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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Section: Discussionmentioning

confidence: 99%

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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“…Their study, as well as that of Bodemann & Hoffman (1976) on red cells, considered the hypothesis that pump turnover rate determined steroid binding rate (the two being related in an inverse manner), but both studies concluded that additional factors were involved. A subsequent study on red cells (Hobbs & Dunham, 1978) led to the conclusion that steroid binding was inhibited by occupation of the external loading sites on the pump by Cs or K, but promoted at a second type of site (possibly the sites which discharge Na after its outward translocation) by Na, Li, or Cs.…”

Section: Discussionmentioning

confidence: 99%

“…For example, in Naor Li-containing solutions, the rate is more rapid than in media in which the predominant monovalent cation is choline (Baker & Willis, 1972). External potassium seems to antagonize the binding of cardiac steroids to human red cells (Glynn, 1957;Gardner & Conlon, 1972;Sachs, 1974;Hobbs and Dunham, 1978); however, Baker & Willis (1972) have reported enhancement of the binding rate when K is added to Na-free solutions surrounding the squid axon. Since understanding the mechanism by which this regulatory effect of external Current address: Laboratory of Neurochemistry, National Institute of Neurological and Com-cations on ouabain binding occurs shows promise of helping to clarify the mechanism by which the Na-K pump operates, this study was designed to examine this phenomenon in more detail.…”

Section: Introductionmentioning

confidence: 99%

Comparative effects of external monovalent cations on sodium pump activity and ouabain inhibition rates in squid giant axon.

Hobbs¹

1982

The Journal of Physiology

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SUMMARY1. A number of external monovalent cations were compared with regard to their effects on Na pump rate and the rate of ouabain inhibition of the pump in squid giant axon.2. External ions which stimulate active Na efflux (K, Rb, and Cs) were found to decrease the rate at which low concentrations of ouabain inhibit the pump, and those ions which inhibit the pump externally (Na and Li) to increase the rate of inhibition.3. In Na-and Li-containing solutions, pump rate appeared to be the major factor in determining the rate of ouabain inhibition regardless of whether K, Cs, or Rb was used to stimulate active Na efflux.4. When choline was substituted for external Na, ouabain inhibition rates were more than twice as rapid when Cs was used as the pump-stimulating cation than when K was activating the pump to a similar level.5. These results suggest that external monovalent cations modulate ouabain inhibition in squid axon at two classes of sites: pump activation sites, and also separate regulatory sites, whose occupation can significantly increase the rate of ouabain inhibition independent of pump turnover rate.

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“…In all studies of this kind, the crucial role of K+ on the regulation of the kinetics of glycoside binding has been demonstrated. The antagonism between external K+ and glycoside binding which was also clearly demonstrated in heart muscle (Akera and Brody, 1978) and the action of external Na+ have been analyzed thoroughly in human red cells (Hobbs and Dunham, 1978). It has been shown that there is no direct competition between external K+ and glycoside for the receptor site.…”

Section: Interaction Of Cardiac Glycosides and Na+k+ Pumpmentioning

confidence: 97%

“…This is due in part to a lowering of the affinity of the external K+ to the system. However, the action of external Na+ is in part also independent of external K+ (Hobbs and Dunham, 1978). In addition, the binding of cardiac glycosides is controlled by a complex interaction of the intracellular ion concentrations of Na+ and K+ (Bodemann et al, 1978).…”

Section: Interaction Of Cardiac Glycosides and Na+k+ Pumpmentioning

confidence: 99%

The current concept for the cardiac glycoside receptor

Bodemann

1981

Clinical Cardiology

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Summary: This brief review emphasizes the significance of the Na+,K+-ATPase or the Na+,K+ pump of the intact membrane as the pharmacological receptor for cardiac glycosides. The properties of this transport enzyme and the regulation of glycoside binding are described. An outline is given of the problems encountered and of the progress made in attempting to correlate the inotropic action of cardiac glycosides with the binding of these drugs to the heart muscle and with the inhibition of the Na+,K+ pump. Furthermore, the correlation of intracellular Ca 2+ activity and Na + concentration with the inhibition of the Na+,K+ pump is discussed. The existence of a digitalis-like endogenous activity may also indicate an important role of the Na+,K+ pump as a receptor for a physiological regulatory control of cardiac contractility.

show abstract

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.

Cited by 18 publications

References 32 publications

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

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

Comparative effects of external monovalent cations on sodium pump activity and ouabain inhibition rates in squid giant axon.

The current concept for the cardiac glycoside receptor

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