Body mass-specific Na⁺-K⁺-ATPase activity in the medullary thick ascending limb: Implications for species-dependent urine concentrating mechanisms

In general, the mammalian whole body mass-specific metabolic rate correlates positively with maximal urine concentration (U_max) irrespective of whether or not the species have adapted to arid or mesic habitat. Accordingly, we hypothesized that the thick ascending limb (TAL) of a rodent with markedly higher whole body mass-specific metabolism than rat exhibits a substantially higher TAL metabolic rate as estimated by Na⁺-K⁺-ATPase activity and Na⁺-K⁺-ATPase α1-gene and protein expression. The kangaroo rat inner stripe of the outer medulla exhibits significantly higher mean Na⁺-K⁺-ATPase activity (~70%) compared with two rat strains (Sprague-Dawley and Munich-Wistar), extending prior studies showing rat activity exceeds rabbit. Furthermore, higher expression of Na⁺-K⁺-ATPase α1-protein (~4- to 6-fold) and mRNA (~13-fold) and higher TAL mitochondrial volume density (~20%) occur in the kangaroo rat compared with both rat strains. Rat TAL Na⁺-K⁺-ATPase α1-protein expression is relatively unaffected by body hydration status or, shown previously, by dietary Na⁺arguing against confounding effects from two unavoidably dissimilar diets: grain-based diet without water (kangaroo rat) or grain-based diet with water (rat). We conclude that higher TAL Na⁺-K⁺-ATPase activity contributes to relationships between whole body mass-specific metabolic rate and high U_maxMore vigorous TAL Na⁺-K⁺-ATPase activity in kangaroo rat than rat may contribute to its steeper Na⁺and urea axial concentration gradients, adding support to a revised model of the urine concentrating mechanism, which hypothesizes a leading role for vigorous active transport of NaCl, rather than countercurrent multiplication, in generating the outer medullary axial osmotic gradient.