Potassium depletion downregulates chloride-absorbing transporters in rat kidney

J Clin Invest. 1998 Mar 1;101(5):1045-54. doi: 10.1172/JCI686.


Potassium depletion (KD) causes renal chloride wasting, suggesting defect(s) in Cl- reabsorption in renal tubules. To determine whether alterations in expression of the major Cl- transporter genes might contribute to the chloride wasting, we analyzed their expression in renal cortex and medulla of animals placed on KD diet. Feeding KD diet to rats resulted in significant hypokalemia at 14 d but not at 6 d. Northern hybridization revealed that mRNA levels for the apical Na-K-2Cl cotransporter in the medulla decreased by 56 and 51% at 6 and 14 d of KD diet, respectively. Functional studies in tubular suspensions from medullary thick ascending limb demonstrated that the Na-K-2Cl cotransporter activity decreased by approximately 45 and approximately 37% at 6 and 14 d of KD diet, respectively. mRNA levels for the thiazide-sensitive Na-Cl cotransporter decreased by 57 and 64% at 6 and 14 d of KD diet. Decreased expression of the apical Na-Cl and the Na-K-2Cl cotransporters became evident at 48 and 72 h of KD, respectively. Urinary chloride excretion increased at 48 h and further increased at 72 h of KD, correlating with suppression of the Na-Cl and the Na-K-2Cl transporters. Our results indicate that increased urinary chloride loss in KD results from suppression of the chloride-absorbing transporters. Downregulation of chloride transporters in KD is an early event and can lead to hypochloremia and subsequently hypovolemia and decreased glomerular filtration rate.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Benzothiadiazines
  • Biological Transport, Active / genetics
  • Blotting, Northern
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Chlorides / metabolism*
  • Diuretics
  • Down-Regulation
  • Gene Expression
  • Hypokalemia / metabolism
  • Ion Transport / genetics
  • Kidney / physiopathology
  • Kidney Cortex / metabolism
  • Kidney Diseases / metabolism*
  • Kidney Medulla / metabolism
  • Kidney Medulla / physiology
  • Male
  • Potassium Deficiency / metabolism*
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Chloride Symporter Inhibitors / pharmacology
  • Sodium Chloride Symporters
  • Sodium-Potassium-Chloride Symporters
  • Symporters*


  • Benzothiadiazines
  • Carrier Proteins
  • Chlorides
  • Diuretics
  • RNA, Messenger
  • Sodium Chloride Symporter Inhibitors
  • Sodium Chloride Symporters
  • Sodium-Potassium-Chloride Symporters
  • Symporters