Body Mass‐Specific Na, K‐ATPase Activity in the Medullary Thick Ascending Limb – Implications for Species‐Dependent Urine Concentrating Mechanisms

Abstract

In general, the mammalian whole body mass‐specific metabolic rate correlates positively with maximal urine concentration (Umax), 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 to 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 (~4–6‐fold) and mRNA (~13‐fold) and higher TAL mitochondrial volume density (~20%) were seen in the kangaroo rat compared to both rat strains. Rat TAL Na, K‐ATPase α1 protein expression is relatively unaffected by body hydration status or, as 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 Umax. With the combination of 70% greater Na, K‐ATPase activity and 50% greater total kidney mass:body mass ratio for the kangaroo rat compared to the rat, and assuming all other factors remain equal, the contribution of TAL Na, K‐ATPase activity to overall whole body metabolism would be about 2.5‐fold greater in the kangaroo rat compared to the rat. More vigorous TAL Na, K‐ATPase activity in the kangaroo rat than in the 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.Support or Funding InformationNIDDK DK083338 (TP) and DK110621 (TR), NSF IOS‐0952885 (TP), Joint DMS/NIGMS‐NSF DMS‐1263943 (TP), APS/NSF Fellowships (MA).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.