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AVP dynamically increases paracellular Na+ permeability and transcellular NaCl transport in the medullary thick ascending limb of Henle’s loop

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Abstract

The medullary thick ascending limb of Henle’s loop (mTAL) is crucial for urine-concentrating ability of the kidney. It is water tight and able to dilute the luminal fluid by active transcellular NaCl transport, fueling the counter current mechanism by increasing interstitial osmolality. While chloride is exclusively transported transcellularly, approx. 50% of sodium transport occurs via the paracellular route, driven by the lumen-positive transepithelial potential. Antidiuretic hormone (AVP) is known to increase active NaCl transport to support collecting duct water reabsorption. Here, we investigated the concomitant effects of AVP on the paracellular properties of mTAL. Freshly isolated mouse mTALs were perfused and electrophysiological transcellular and paracelluar properties were assessed in a paired fashion before and after AVP stimulation. In addition, the same parameters were measured in mice on a water-restricted (WR) or water-loaded (WL) diet for 5 days. Acute ex vivo stimulation as well as long-term in vivo water restriction increased equivalent short circuit current as a measure of active transcellular NaCl transport. Intriguingly, in both experimental approaches, this was accompanied by markedly increased paracellular Na+ selectivity. Thus, AVP is able to acutely regulate paracellular cation selectivity in parallel to transcellular NaCl transport, allowing balanced paracellular Na+ absorption under an increased transepithelial driving force.

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Acknowledgements

We thank the Department of Animal Care of the Christian-Albrechts-Universität Kiel (CAU) for their excellent support in breeding and animal handling. We thank T. Stegmann and R. Lingg for high-quality technical assistance.

Grants

The project was kindly supported by the Christian-Albrechts-Universität zu Kiel (CAU) funding to N.H., M.B., S.S., and A.P. and by the Danish Medical Research Foundation (0602-02390B) to J.L. and R.M.

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Authors and Affiliations

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

    Nina Himmerkus, Allein Plain, Svenja R. Sonntag & Markus Bleich

  2. Department of Biomedicine, Physiology, Aarhus University, Aarhus, Denmark

    Rita D. Marques & Jens Leipziger

  3. Department of Nephrology, Charité-Universitätsmedizin Berlin, Berlin, Germany

    Alexander Paliege

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  1. Nina Himmerkus
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  2. Allein Plain
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Correspondence to Nina Himmerkus.

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Nina Himmerkus and Allein Plain contributed equally. Jens Leipziger and Markus Bleich contributed equally.

This article is published as part of the Special Issue on “Physiology, pathophysiology and clinical impact of claudins.”

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Himmerkus, N., Plain, A., Marques, R.D. et al. AVP dynamically increases paracellular Na+ permeability and transcellular NaCl transport in the medullary thick ascending limb of Henle’s loop. Pflugers Arch - Eur J Physiol 469, 149–158 (2017). https://doi.org/10.1007/s00424-016-1915-5

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