Volume-sensitive Cl-dependent K transport in human erythrocytes.

Passive K fluxes, measured with 86Rb, were investigated in osmotically swollen human erythrocytes. K influx and efflux increased progressively with increased hypotonicity up to 167 mosmol/kg. No increase in K flux was seen when NO3 or methylSO4 were substituted for Cl. Substitution of choline or N-methylglucamine for external Na reduced the K flux in swollen cells by only 22%, compared with a 60% reduction in euvolumic cells. However, the magnitude of this Na-dependent component was slightly, but significantly, higher in swollen cells. The presence of Na-dependent K influx in swollen cells was confirmed by measurements of Na influx demonstrating a K-dependent Na influx of similar magnitude in isovolumic and swollen cells. The volume-sensitive K flux was inhibited by bumetanide, but significantly less so than was Cl-dependent flux in isovolumic cells (half-maximal inhibition at 1.0 X 10(-4) vs. 5.8 X 10(-7) M). Kinetic analysis revealed that Cl-dependent K influx had a lower affinity for external K in swollen cells than in euvolumic cells (Km was 29.8 vs. 6.1 mM). The increased K flux in swollen cells was found to be transient, decreasing substantially and reverting back to a predominantly Na-dependent and more bumetanide-sensitive form after 2 h. The results indicate that swelling of human erythrocytes activates a transient Cl-dependent K flux that differs significantly from that in isovolumic cells in that it is less Na dependent, less sensitive to bumetanide, and has a lower affinity for K. Na-K cotransport is either unaffected or slightly increased in swollen cells. The altered flux in swollen cells would thermodynamically favor a volume-regulatory KCl efflux.