POTASSIUM-DEPLETION DOWN-REGULATES CHLORIDE-ABSORBING TRANSPORTERS INRAT-KIDNEY

Potassium depletion (KD) causes renal chloride wasting, suggesting def ect(s) in Cl- reabsorption in renal tubules. To determine whether alte rations in expression of the major Cl- transporter genes might contrib ute to the chloride wasting, we analyzed their expression in renal cor tex 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 h ybridization revealed that mRNA levels for the apical Na-K-2Cl cotrans porter in the medulla decreased by 56 and 51% at 6 and 14 d of KD diet , respectively. Functional studies in tubular suspensions from medulla ry thick ascending limb demonstrated that the Na-K-2Cl cotransporter a ctivity decreased by similar to 45 and similar to 37% at 6 and 14 d of KD diet, respectively. mRNA levels for the thiazide-sensitive Na-CI c otransporter decreased by 57 and 64% at 6 and 14 d of KD diet, Decreas ed expression of the apical Na-CI and the Na-K-2Cl cotransporters beca me evident at 48 and 72 h of KD, respectively. Urinary chloride excret ion increased at 48 h and further increased at 72 h of KD, correlating with suppression of the Na-CI and the Na-K-2Cl transporters. Our resu lts indicate that increased urinary chloride loss in KD results from s uppression of the chloride-absorbing transporters, Downregulation of c hloride transporters in KD is an early event and can lead to hypochlor emia and subsequently hypovolemia and decreased glomerular filtration rate.