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

Plain, A., Wulfmeyer, V. C., Milatz, S., Klietz, A., Hou, J. H., Bleich, Markus and Himmerkus, N. (2016) Corticomedullary difference in the effects of dietary Ca2+ on tight junction properties in thick ascending limbs of Henle’s loop Pflügers Archiv - European Journal of Physiology, 468 (2). pp. 293-303. DOI 10.1007/s00424-015-1748-7.

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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 a (TM) aEuro parts per thousand 10(-4) cm/s and from 4.8 +/- 0.5 to 3.0 +/- 0.2 center dot 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+.

Document Type: Article
Additional Information: Times Cited: 0 Plain, Allein Wulfmeyer, Vera C. Milatz, Susanne Klietz, Adrian Hou, Jianghui Bleich, Markus Himmerkus, Nina
Keywords: Nephron, Calcium, Ion Transport, Claudin, Paracellular permeability, Microperfusion
Research affiliation: OceanRep > The Future Ocean - Cluster of Excellence > FO-R08
Kiel University > Kiel Marine Science
OceanRep > The Future Ocean - Cluster of Excellence
OceanRep > The Future Ocean - Cluster of Excellence > FO-R04
Kiel University
Refereed: Yes
DOI etc.: 10.1007/s00424-015-1748-7
ISSN: 0031-6768
Projects: Future Ocean
Date Deposited: 27 Feb 2017 08:12
Last Modified: 24 Sep 2019 03:48
URI: http://eprints.uni-kiel.de/id/eprint/36263

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