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J Physiol Vol 243, Issue 1 pp 243-266
Copyright © 1974 by The Physiological Society
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Thallium and the sodium pump in human red cells

J. D. Cavieres and J. C. Ellory

1. Thallium (Tl) inhibits the ouabain-sensitive K influx in human red cells in high-Na medium. At 1 mM external K concentration [Ko], the ouabain-sensitive K influx decreases steadily with increasing Tl concentration, up to 0·9 mM outside; at 0·17 mM-Ko, however, Tl stimulates the ouabain-sensitive K influx below 0·1 mM-Tlo and inhibits it at higher concentrations.

2. In a K-free medium in which all except 5 mM-Na is replaced by choline, and into which red cells show zero control ouabain-sensitive Na efflux, Tl is able to support ouabain-sensitive Na efflux up to 2·1 m-mole/l. cells.hr following a sigmoid activation curve which is half-maximal between 0·03 and 0·05 mM-Tlo and that follows two-site kinetics up to 0·1 mM-Tlo. Beyond 0·15 mM-Tlo, the Tl-activated ouabain-sensitive Na efflux attained is inhibited slightly.

3. When the ouabain-sensitive Na efflux is measured at 5 mM-Nao and 5 mM-Ko, increasing concentrations of Tl have little effect on it, 0·9 mM-Tlo inhibiting by some 14%; in similar conditions, the ouabain-sensitive K influx is inhibited by about 40%.

4. The dependence of ouabain-sensitive K influx on external K concentration at 5 mM-Nao, which follows a slightly sigmoid curve in the absence of Tl, changes to hyperbolic at 0·06 mM-Tlo at the same time that ouabain-sensitive K influx is inhibited. The fitted Vmax values for ouabain-sensitive K influx are the same in the presence and in the absence of 0·06 mM-Tlo.

5. In high-Na cells, loaded by nystatin treatment, the ouabain-sensitive K influx measured at 0·2 mM-Nao follows a hyperbolic curve between 0·05 and 0·4 mM-Ko, and is inhibited by Tl in a strictly competitive fashion.

6. The effects of Tl on ouabain-sensitive Na efflux and ouabain-sensitive K influx are interpreted in terms of a high-affinity substitution for K at the external K sites of the Na pump and suggest that in human red cells Tl can be actively transported inwards in exchange for internal Na.

7. Thallium can inhibit about 25% of the ouabain-insensitive Na efflux into 5 mM-Nao and part of this inhibition occurs with a high Tl-affinity; the ouabain-insensitive K influx is inhibited by Tl both in high-Na and in 5 mM-Na medium, but with a different concentration dependence than the ouabain-insensitive Na efflux.







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