Potassium transport in the rabbit renal proximal tubule: effects of barium, ouabain, valinomycin, and other ionophores.

Potassium fluxes in a suspension of rabbit proximal tubules were monitored using a potassium-sensitive extracellular electrode. Ouabain (10(-4) M) and barium (5 mM) were used to selectively quantitate the potassium efflux pathway (105 +/- 5 nmol K+ X mg protein-1 X min-1) and the sodium pump-related potassium influx (108 +/- 7), respectively. These equal and opposite fluxes suggest that potassium accumulation in the cell occurs mainly through the sodium pump and that potassium efflux occurs mainly through barium-sensitive potassium channels. Thus the activity of the sodium pump (Na,K-ATPase) in the basolateral membrane of the proximal tubule is balanced by the efflux of potassium, presumably across the basolateral membrane, which has a high potassium permeability. In addition, the effect of valinomycin and other ionophores was examined on potassium fluxes and several metabolic parameters [oxygen consumption (QO2), ATP content]. The addition of valinomycin to the tubules produced a net efflux of potassium which was quantitatively equivalent to the efflux produced by the addition of ouabain. The valinomycin-induced efflux was mainly due to the activity of valinomycin as a mitochondrial uncoupler, which indirectly inhibited the sodium pump by allowing a rapid reduction of the intracellular ATP. Amphotericin, nystatin, and monensin all produced large net releases of intracellular potassium. The action of the ionophores could be localized to the plasma or mitochondrial membrane and classified into three groups, as follows: those which demonstrated full mitochondrial uncoupler activity (FCCP, valinomycin), those which had no uncoupler activity (amphotericin B, nystatin); and those which displayed partial uncoupler activity (monensin, nigericin).