title: AVP dynamically increases paracellular Na+permeability and transcellular NaCl transport in the medullary thick ascending limb of Henle's loop.
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.
authors.affiliation: Institute of Physiology, Christian-Albrechts-University, Olshausenstr. 40, 24098, Kiel, Germany. n.himmerkus@physiologie.uni-kiel.de.
authors.forename: Nina
authors.identifier: 0000-0002-2910-6728
authors.initials: N
authors.lastname: Himmerkus
authors.affiliation: Institute of Physiology, Christian-Albrechts-University, Olshausenstr. 40, 24098, Kiel, Germany.
authors.forename: Allein
authors.initials: A
authors.lastname: Plain
authors.affiliation: Department of Biomedicine, Physiology, Aarhus University, Aarhus, Denmark.
authors.forename: Rita D
authors.initials: RD
authors.lastname: Marques
authors.affiliation: Institute of Physiology, Christian-Albrechts-University, Olshausenstr. 40, 24098, Kiel, Germany.
authors.forename: Svenja R
authors.initials: SR
authors.lastname: Sonntag
authors.affiliation: Department of Nephrology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Paliege
authors.affiliation: Department of Biomedicine, Physiology, Aarhus University, Aarhus, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Leipziger
authors.affiliation: Institute of Physiology, Christian-Albrechts-University, Olshausenstr. 40, 24098, Kiel, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Bleich
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology*; D006801:Humans; D007679:Kidney Medulla / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D010539:Permeability; D012964:Sodium / Q000378:metabolism*; D012965:Sodium Chloride / Q000378:metabolism*; D014667:Vasopressins / Q000378:metabolism*
chemical_list: D014667:Vasopressins; D012965:Sodium Chloride; D012964:Sodium
keywords: Claudins; Concentration mechanism; Outer medulla; Sodium transport; Tight junction