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

Abstract

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 μM, corresponding to concentrations of 9–23 μM 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 (UKV) from 0.85 ± 0.15 to 0.05 ± 0.01 μmol/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 UKV from 7.5 ± 0.7 to 1.3 ± 0.1 μmol/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 UKV less, from 6.1 ± 0.6 to 3.0 ± 0.8 μmol/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+.