K+ secretion in the rat kidney: Na+ channel-dependent and -independent mechanisms

Renal Na(+) and K(+) excretion was measured in rats with varying dietary K(+) intake. The requirement for channel-mediated distal nephron Na(+) reabsorption was assessed by infusing the animals with the K(+)-sparing diuretic amiloride via osmotic minipumps. At infusion rates of 2 nmol/min, the concentration of amiloride in the urine was 38 microM, corresponding to concentrations of 9-23 microM in the distal tubular fluid, sufficient to block >98% of Na(+) transport through apical Na(+) channels (ENaC). With a control K(+) intake (0.6% KCl), amiloride reduced K(+) excretion rates (U(K)V) from 0.85 +/- 0.15 to 0.05 +/- 0.01 micromol/min during the first 2 h of infusion, suggesting that distal nephron K(+) secretion was completely dependent on the activity of Na(+) channels. When K(+) intake was increased by feeding overnight with a diet containing 10% KCl, amiloride reduced U(K)V from 7.5 +/- 0.7 to 1.3 +/- 0.1 micromol/min despite an increased plasma K(+) of 9 mM, again suggesting a major but not exclusive role for the Na(+) channel-dependent pathway of K(+) secretion. The maximal measured rates of amiloride-sensitive K(+) excretion correspond well with estimates based on apical K(+) channel activity in distal nephron segments. However, when the animals were adapted to the high-K(+) diet for 7-9 days, the diuretic decreased U(K)V less, from 6.1 +/- 0.6 to 3.0 +/- 0.8 micromol/min, indicating an increasing fraction of K(+) excretion that was independent of Na(+) channels. This indicates the upregulation of a Na(+) channel-independent mechanism for secreting K(+).