Thallium and the sodium pump in human red cells

Abstract

1. Thallium (Tl) inhibits the ouabain-sensitive K influx in human red cells in high-Na medium. At 1 mM external K concentration [K(o)], the ouabain-sensitive K influx decreases steadily with increasing Tl concentration, up to 0.9 mM outside; at 0.17 mM-K(o), however, Tl stimulates the ouabain-sensitive K influx below 0.1 mM-Tl(o) 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-Tl(o) and that follows two-site kinetics up to 0.1 mM-Tl(o). Beyond 0.15 mM-Tl(o), the Tl-activated ouabain-sensitive Na efflux attained is inhibited slightly.3. When the ouabain-sensitive Na efflux is measured at 5 mM-Na(o) and 5 mM-K(o), increasing concentrations of Tl have little effect on it, 0.9 mM-Tl(o) 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-Na(o), which follows a slightly sigmoid curve in the absence of Tl, changes to hyperbolic at 0.06 mM-Tl(o) at the same time that ouabain-sensitive K influx is inhibited. The fitted V(max) values for ouabain-sensitive K influx are the same in the presence and in the absence of 0.06 mM-Tl(o).5. In high-Na cells, loaded by nystatin treatment, the ouabain-sensitive K influx measured at 0.2 mM-Na(o) follows a hyperbolic curve between 0.05 and 0.4 mM-K(o), 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-Na(o) 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.