Thallium and the sodium pump in human red cells

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Abstract
1. Thallium (Tl) inhibits the ouabain‐sensitive K influx in human red cells in high‐Na medium. At 1 m M external K concentration [Ko], the ouabain‐sensitive K influx decreases steadily with increasing Tl concentration, up to 0·9 m M outside; at 0·17 m M‐Ko, however, Tl stimulates the ouabain‐sensitive K influx below 0·1 m M‐Tlo and inhibits it at higher concentrations.2. In a K‐free medium in which all except 5 m M‐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 m M‐Tlo and that follows two‐site kinetics up to 0·1 m M‐Tlo. Beyond 0·15 m M‐Tlo, the Tl‐activated ouabain‐sensitive Na efflux attained is inhibited slightly.3. When the ouabain‐sensitive Na efflux is measured at 5 m M‐Nao and 5 m M‐Ko, increasing concentrations of Tl have little effect on it, 0·9 m M‐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 m M‐Nao, which follows a slightly sigmoid curve in the absence of Tl, changes to hyperbolic at 0·06 m M‐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 m M‐Tlo.5. In high‐Na cells, loaded by nystatin treatment, the ouabain‐sensitive K influx measured at 0·2 m M‐Nao follows a hyperbolic curve between 0·05 and 0·4 m M‐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 m M‐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 m M‐Na medium, but with a different concentration dependence than the ouabain‐insensitive Na efflux.