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1 Department of Anatomy, The Catholic University of Korea, Seoul, Korea, Republic of
2 Department of Medicine, University of Florida College of Medicine, Gainesville, Florida, USA
3 Deparment of Internal Medicine, The Catholic University of Korea, Seoul, Korea, Republic of
4 Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, USA
5 Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
* To whom correspondence should be addressed. E-mail: jinkim{at}catholic.ac.kr.
Urea transport in the kidney is mediated by a family of transporter proteins that includes the renal urea transporter (UT-A) and the erythrocyte urea transporter (UT-B). The purpose of this study was to determine the location of the urea transporter isoforms in the mouse kidney and to examine the effects of prolonged potassium depletion on the expression and distribution of these transporters, by ultrastructural immunocytochemistry. C57BL6 mice were fed a low-potassium diet for two weeks and control animals received normal chow. After two weeks on a low-potassium diet, urine volume increased and urine osmolality decreased (833 ± 30 vs. 1,919 ± 174 mOsm/kg H2O), as previously demonstrated. Kidneys were processed for immunocytochemistry with antibodies against UT-A1 (L446), UT-A1 and UT-A2 (L194), UT-A3 (Q2), and UT-B. In normal mice, UT-A1 and UT-A3 were expressed mainly in the cytoplasm of the terminal inner medullary collecting duct (IMCD). UT-A2 immunoreactivity was observed mainly on the basolateral membrane of the type 1 epithelium of the descending thin limb (DTL) of short-looped nephrons. The intensity of UT-A1 and UT-A3 immunoreactivity in the IMCD was markedly reduced in potassium-depleted mice. In contrast, there was a significant increase in UT-A2 immunoreactivity in the DTL. The intensity of UT-B immunoreactivity in the descending vasa recta (DVR) was reduced in potassium-depleted animals compared with controls. In control animals, UT-B immunoreactivity was predominantly observed in the plasma membrane, whereas in potassium-depleted mice, it was mainly observed in cytoplasmic granules in endothelial cells of the DVR. In summary, potassium depletion is associated with reduced expression of UT-A1, UT-A3, and UT-B, but increased expression of UT-A2. We conclude that reduced expression of urea transporters may play a role in the impaired urine-concentrating ability associated with potassium deprivation.
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