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(+).
Frindt
Gustavo
G
Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, New York 10065, USA.
Palmer
Lawrence G
LG
D000222:Adaptation, Physiological; D000450:Aldosterone / Q000008:administration & dosage; D000584:Amiloride / Q000008:administration & dosage / Q000652:urine; D000818:Animals; D001692:Biological Transport; D004039:Diet, Sodium-Restricted; D053503:Epithelial Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005919:Glomerular Filtration Rate; D015918:Infusion Pumps, Implantable; D007700:Kinetics; D009318:Natriuresis; D009399:Nephrons / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000097:blood / Q000378:metabolism* / Q000652:urine; D015221:Potassium Channels / Q000378:metabolism*; D017419:Potassium, Dietary / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000097:blood / Q000378:metabolism* / Q000652:urine; D026941:Sodium Channel Blockers / Q000008:administration & dosage / Q000652:urine; D012982:Sodium, Dietary / Q000378:metabolism; D013997:Time Factors; D014563:Urodynamics
D053503:Epithelial Sodium Channels; D015221:Potassium Channels; D017419:Potassium, Dietary; D026941:Sodium Channel Blockers; D012982:Sodium, Dietary; D000450:Aldosterone; D000584:Amiloride; D012964:Sodium; D011188:Potassium