Abstract
In the renal proximal tubule (PT) and the intestine, passive paracellular Ca2+ reabsorption has been linked to active Na+ reabsorption via the Na+‐H+ exchanger type 3 (NHE3). Whole body NHE3 knockout mice show reduced intestinal Ca2+ absorption and significantly higher urinary Ca2+ excretion. To isolate the kidney‐specific role of NHE3 in this process, we examined Ca2+ handling in our recently generated kidney tubule‐specific NHE3 knockout mice [NHE3loxloxPax8Cre; Am J Physiol Renal Physiol. 2015;308(12):F1409‐20]. Twenty‐four‐hour metabolic cage experiments did not show significant differences in urinary Ca2+ excretion between genotypes on standard diet (control: 10.5 ± 1.4 μmol; NHE3loxloxPax8Cre: 11.3 ± 1.7 μmol, NS) in conjunction with normal plasma Ca2+ concentrations (control: 1.27 mM ± 0.01 mM; NHE3loxloxPax8Cre: 1.28 ± 0.01 μmol, NS). A high (4%) NaCl diet increased urinary Ca2+ excretion to a similar degree in both genotypes (control: 29.8 ± 6.3; NHE3loxloxPax8Cre: 28.9± 5.5, NS). Analysis of whole kidney samples for proteins involved in renal Ca2+ handling by RT‐qPCR indicated increased expression of transient receptor potential cation channel subfamily V member 5, TRPV5, and Na+‐Cl− cotransporter, NCC (1.34‐fold and 1.44‐fold, respectively, P < 0.05) in NHE3loxloxPax8Cre vs control mice. Similar changes were detected by immunoblotting (TRPV5: 1.57‐fold; NCC: 1.27‐fold; P < 0.05). Our results indicate intact Ca2+ homeostasis in kidney‐specific NHE3 knockout mice. We speculate that compensatory mechanisms exist; however, our results also suggest that PT Ca2+ reabsorption for long‐term Ca2+ homeostasis plays a less important role than previously assumed.Support or Funding InformationFunding to R.A.F. is provided by the Novo Nordisk Foundation, the Lundbeck Foundation and Danish Medical Research Council. T.R. is supported by NIDDK 1R01DK110621.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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