Abstract
SLC4A11 is a multifunctional membrane transporter involved with H+ transport, NH 3 and alkaline pH stimulated H+ transport, and water transport. The role of SLC4A11 in the kidney is not well understood. A prior study has shown that in murine kidney, SLC4A11/LacZ staining is primarily in the long‐looped descending thin limb (DTL) as determined by colocalization with aquaporin 1 (AQP1), a protein that is expressed in some, but not all, descending thin limb segments. Using a previously characterized polyclonal antibody, we demonstrate the selective expression of SLC4A11 in the upper DTLs (which are AQP1‐positive) in the outer medulla and inner medulla with little or no expression in the lower DTLs (which are AQP‐1‐null). SLC4A11 also colocalized with AQP1 and the urea transporter UT‐B in the mouse descending vasa recta, but was absent in mouse and rat ascending vasa recta. Mouse, but not rat, outer medullary collecting duct cells also labeled for SLC4A11. Our results are compatible with the hypothesis that in the inner stripe of the outer medulla, SLC4A11 plays a role in the countercurrent transport of ammonia absorbed from the outer medullary thick ascending limb and secreted into the long‐looped DTLs. SLC4A11 can potentially modulate the rate of ammonia transport in the mouse outer medullary collecting duct. Our data suggest functionally unique SLC4A11 pathways in mouse and rat and complement previous studies of DTL Na+, urea and water permeability indicating that the upper and lower DTLs of long‐looped nephrons are functionally distinct.
Highlights
SLC4A11 is a member of the SLC4 bicarbonate transporter family whose members are expressed in multiple organs and play key roles in systemic acid–base balance, transepithelial transport, intracellular/extracellular ion homeostasis, and cell function (Parker and Boron 2013; Kurtz 2014; Huynh et al 2018)
aquaporin 1 (AQP1) is expressed in the upper portions of descending segments of rodent long-looped nephrons that pass through the inner stripe of the outer medulla (ISOM) and outer inner medulla (IM) (“upper descending thin limb (DTL)”) (Dantzler et al 2014; Nawata et al 2014) (Fig. 2)
The “lower DTL” segments, which are present in both the outer medulla (OM) and IM, do not express detectable AQP1 and include both long-looped DTLs and descending segments that have been recently defined in the mouse as the intermediate loop DTLs (Kim et al 2016)
Summary
SLC4A11 is a member of the SLC4 bicarbonate (and carbonate) transporter family whose members are expressed in multiple organs and play key roles in systemic acid–base balance, transepithelial transport, intracellular/extracellular ion homeostasis, and cell function (Parker and Boron 2013; Kurtz 2014; Huynh et al 2018). Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. SLC4A11: A Candidate Transporter in Renal Ammonia Recycling thought to be a multifunction transporter that mediates H+ flux, NH3 and alkaline pH stimulated H+ transport, and water flux in the presence of an osmotic gradient (Vilas et al 2013; Kao et al 2015, 2016; Zhang et al 2015; Loganathan et al 2016; Myers et al 2016). While no renal phenotype has been reported, patients with mutated SLC4A11 exhibit an anion gap of +68 (with respect to NaCl and KCl), which is compatible with a defect in urine ammonia excretion (Liskova et al 2015)
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