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Corticomedullary difference in the effects of dietary Ca2+ on tight junction properties in thick ascending limbs of Henle’s loop

  • Organ physiology
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Abstract

The thick ascending limb of Henle’s loop (TAL) drives an important part of the reabsorption of divalent cations. This reabsorption occurs via the paracellular pathway formed by the tight junction (TJ), which in the TAL shows cation selectivity. Claudins, a family of TJ proteins, determine the permeability and selectivity of this pathway. Mice were fed with normal or high-Ca2+ diet, and effects on the reabsorptive properties of cortical and medullary TAL segments were analysed by tubule microdissection and microperfusion. Claudin expression was investigated by immunostaining and quantitative PCR. We show that the TAL adapted to high Ca2+ load in a sub-segment-specific manner. In medullary TAL, transcellular NaCl transport was attenuated. The transepithelial voltage decreased from 10.9 ± 0.6 mV at control diet to 8.3 ± 0.5 mV at high Ca2+ load, thereby reducing the driving force for Ca2+ and Mg2+ uptake. Cortical TAL showed a reduction in paracellular Ca2+ and Mg2+ permeabilities from 8.2 ± 0.7 to 6.2 ± 0.5 ∙ 10−4 cm/s and from 4.8 ± 0.5 to 3.0 ± 0.2 · 10−4 cm/s at control and high-Ca2+ diet, respectively. Expression, localisation and regulation of claudins 10, 14, 16 and 19 differed along the corticomedullary axis: Towards the cortex, the main site of divalent cation reabsorption in TAL, high-Ca2+ intake led to a strong upregulation of claudin-14 within TAL TJs while claudin-16 and -19 were unaltered. Towards the inner medulla, only claudin-10 was present in TAL TJ strands. In summary, high-Ca2+ diet induced a reduction of divalent cation reabsorption via a diminution of NaCl transport and driving force in mTAL and via decreased paracellular permeabilities in cTAL. We reveal an important regulatory pattern along the corticomedullary axis and improve the understanding how the kidney disposes of detrimental excess Ca2+.

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Acknowledgments

We thank Kerim Mutig (Charité, Berlin) for kindly providing the NKCC2 antibody.

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

This study was funded by the Christian-Albrechts-University Kiel.

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Authors and Affiliations

  1. Institute of Physiology, Christian-Albrechts-University Kiel, Olshausenstraße 40, Kiel, 24098, Germany

    Allein Plain, Vera C. Wulfmeyer, Susanne Milatz, Adrian Klietz, Markus Bleich & Nina Himmerkus

  2. Washington University Renal Division, St. Louis, MO, USA

    Jianghui Hou

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  1. Allein Plain
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  2. Vera C. Wulfmeyer
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Correspondence to Nina Himmerkus.

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Table S1

Primers applied for Real Time PCR (DOC 29 kb)

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Plain, A., Wulfmeyer, V.C., Milatz, S. et al. Corticomedullary difference in the effects of dietary Ca2+ on tight junction properties in thick ascending limbs of Henle’s loop. Pflugers Arch - Eur J Physiol 468, 293–303 (2016). https://doi.org/10.1007/s00424-015-1748-7

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  • DOI: https://doi.org/10.1007/s00424-015-1748-7

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