Local pH domains regulate NHE3 mediated Na+ reabsorption in the renal proximal tubule.
Local pH domains regulate NHE3 mediated Na+ reabsorption in the renal proximal tubule. Am J Physiol Renal Physiol. 2014 Oct 8; Authors: Brasen JC, Burford JL, McDonough AA, Holstein-Rathlou NH, Peti-Peterdi J Abstract The proximal tubule Na(+)/H(+) exchanger 3 (NHE3), located in the apical dense microvilli (brush border), plays a major role in the reabsorption of NaCl and water in the renal proximal tubule. In response to a rise in blood pressure NHE3 redistributes in the plane of the plasma membrane to the base of the brush border where NHE3 activity is reduced. This NHE3 redistribution is assumed to provoke pressure natriuresis, however, it is unclear how NHE3 redistribution per se reduces NHE3 activity. To investigate if the distribution of NHE3 in the brush border can change reabsorption rate, we constructed a spatiotemporal mathematical model of NHE3 mediated Na(+) reabsorption across a proximal tubule cell and compared the model results with in vivo experiments in rats. The model predicts that when NHE3 is localized exclusively at the base of the brush border it creates local pH microdomains that reduce NHE3 activity by>30%. We tested the model's prediction experimentally: rat kidney cortex was loaded with the pH sensitive fluorescent dye BCECF and cells of the proximal tubule were imaged in vivo using confocal fluorescence microscopy before and after increasing blood pressure by ~ 50 mmHg. The experimental results support the model by demonstra...
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