Age-related changes in renal function, membrane metabolism, transporter activity and abundance in hypokalemic Fischer 344 x Brown-Norway F1 rats

Date

1998-05

Journal Title

Journal ISSN

Volume Title

Publisher

Texas Tech University

Abstract

Potassium depletion (-K) is a common electrolyte abnormality in elderly humans, occurring as a consequence of diuretic use or poor oral intake. The efifects of diet-induced hypokalemia on renal function, cortical brush-border (BBM) and basolateral membrane (BLM) protein and lipid metabolism, transporter activity and abundance were examined in non-obese male Fischer 344 x Brown-Norway Fl rats of 4 mo and 30 mo of age. These experiments were designed to examine whether age-associated changes occur in these parameters and whether the aged animals respond differently to potassium depletion as compared tq the young animals. Western blot analysis of the al-subunit Na,K-ATPase and sodium hydrogen exchanger-1 (NHE-1) in BLM as well as NHE-3 in BBM was determined. Adenosine triphosphatase (ATPase) activity was measured in membrane vesicles and three microdissected segments of the nephron (proximal convoluted tubule [PCT], cortical collecting tubule [CCT], and medullary collecting tubule [MCT]). In both age groups, potassium depletion decreased total body potassium content; plasma ldosterone fell while plasma cholesterol and muscle Na concentration increased. Hypokalemia caused a urinary concentrating defect in addition to a rise in urinary excretion of ammonium, titratable acid and phosphate. Blood urea nitrogen, plasma bicarbonate, and glucose increased significantly with -K, but only in the senescent rats. Fractional excretion of Na and CI also increased, but only in the young hypokalemic animals. The control aged rats had a 35% lower plasma aldosterone and a 42% higher plasma cholesterol as compared to their control young counterparts. Protein and phospholipid concentration and biosynthesis of BBM and BLM were measured after U-^14 C-leucine and 32^P incorporation (24 hr), respectively. In the young animals, hypokalemia increased protein concentration in both membranes, but BLM biosynthesis fell. In the senescent group, hypokalemia did not change protein concentration, however, it decreased protein biosynthesis in both membranes. Phospholipid concentration and biosynthesis of BBM and BLM were altered selectively, both with aging and with potassium depletion. In BLM, the al-subunit Na,K-ATPase and NHE-1 protein abundance did not change with -K in either age group. In BBM, hypokalemia increased NHE-3 protein abundance only in the young animals. In the senescent rats, the rise in NHE-3 protein abundance to -K was blunted. Hypokalemia increased Na,K-ATPase activity in both BLM vesicles and all of the microdissected nephron segments. H, K-ATPase activity increased with -K in both CCT and MCT. In hypokalemic rats, H-ATPase activity in collecting tubule decreased as compared to the control. Aging selectively blunted the response of Na,K-ATPase activity in CCT and H-ATPase activity in MCT during hypokalemia. These results show that significant age-related changes occur in renal function, membrane protein and lipid metabolism, transporter activity and abundance during potassium depletion. These alterations likely explain some of changes in renal tubular function seen with hypokalemia. These findings may have important implications for elderly humans who either receive diuretics or have poor dietary intake.

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Keywords

Proteinuria, Hypokalemia, Renal tubular transport, Potassium, Kidneys, Potassium deficiency diseases

Citation