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Role of NHE3 in renal calcium handling
Author(s) -
Poulsen Søren Brandt,
Rieg Jessica Dominguez,
Rieg Timo,
Fenton Robert A.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.624.22
Subject(s) - reabsorption , chemistry , endocrinology , medicine , kidney , excretion , homeostasis , distal convoluted tubule , paracellular transport , calcium , cotransporter , calcium metabolism , sodium , biology , biochemistry , permeability (electromagnetism) , organic chemistry , membrane
In the renal proximal tubule (PT) and the intestine, passive paracellular Ca 2+ reabsorption has been linked to active Na + reabsorption via the Na + ‐H + exchanger type 3 (NHE3). Whole body NHE3 knockout mice show reduced intestinal Ca 2+ absorption and significantly higher urinary Ca 2+ excretion. To isolate the kidney‐specific role of NHE3 in this process, we examined Ca 2+ handling in our recently generated kidney tubule‐specific NHE3 knockout mice [NHE3 loxloxPax8Cre ; Am J Physiol Renal Physiol. 2015;308(12):F1409‐20]. Twenty‐four‐hour metabolic cage experiments did not show significant differences in urinary Ca 2+ excretion between genotypes on standard diet (control: 10.5 ± 1.4 μmol; NHE3 loxloxPax8Cre : 11.3 ± 1.7 μmol, NS ) in conjunction with normal plasma Ca 2+ concentrations (control: 1.27 mM ± 0.01 mM; NHE3 loxloxPax8Cre : 1.28 ± 0.01 μmol, NS ). A high (4%) NaCl diet increased urinary Ca 2+ excretion to a similar degree in both genotypes (control: 29.8 ± 6.3; NHE3 loxloxPax8Cre : 28.9± 5.5, NS ). Analysis of whole kidney samples for proteins involved in renal Ca 2+ 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 NHE3 loxloxPax8Cre vs control mice. Similar changes were detected by immunoblotting (TRPV5: 1.57‐fold; NCC: 1.27‐fold; P < 0.05). Our results indicate intact Ca 2+ homeostasis in kidney‐specific NHE3 knockout mice. We speculate that compensatory mechanisms exist; however, our results also suggest that PT Ca 2+ reabsorption for long‐term Ca 2+ homeostasis plays a less important role than previously assumed. Support or Funding Information Funding 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 .