Jens Georg Leipziger

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

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  • Nina Himmerkus, Univ Kiel, University of Kiel, Inst Physiol
  • ,
  • Allein Plain, Univ Kiel, University of Kiel, Inst Physiol
  • ,
  • Rita D. Marques
  • ,
  • Svenja R. Sonntag, Univ Kiel, University of Kiel, Inst Physiol
  • ,
  • Alexander Paliege, Charite Univ Med Berlin, Free University of Berlin, Charite Medical University of Berlin, Humboldt University of Berlin, Dept Nephrol
  • ,
  • Jens Leipziger
  • Markus Bleich, Univ Kiel, University of Kiel, Inst Physiol

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.

Original languageEnglish
JournalPflügers Archiv - European Journal of Physiology
Volume469
Issue1
Pages (from-to)149-158
Number of pages10
ISSN0031-6768
DOIs
Publication statusPublished - Jan 2017

    Research areas

  • Claudins, Concentration mechanism, Outer medulla, Tight junction, Sodium transport, TIGHT JUNCTION PROTEINS, RABBIT KIDNEY, ADENYLATE-CYCLASE, COTRANSPORTER NKCC2, KINASE-A, IN-VIVO, VASOPRESSIN, MOUSE, PHOSPHORYLATION, EXPRESSION

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