Journal
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
Volume 28, Issue 1, Pages 130-139Publisher
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2015070734
Keywords
-
Categories
Funding
- European Renal Association - European Dialysis and Translpantation Association LTF grant [141-2013]
- Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)
- Cardiovasculaire, Obesite, Rein, Diabete-Domaines d'Interet Majeur from the Region Ile de France
- la Fondation pour la Recherche Medicale grant [DEA20100619499]
- Canadian Institutes of Health Research
- Institut National de la Sante et de la Recherche Medicale
- Centre National de la Recherche Scientifique
- l'Agence Nationale de la Recherche [BLANC 14-CE12-0013-01/HYPERSCREEN, BLANC 2012-R13011KK]
- grant CHLORBLOCK from the Initiative d'excellence Sorbonne Paris Cite
- grant Evaluation-Orientation de la Cooperation Scientifique/CONICYT France-Chile
- Else Kroner Foundation
- [HU 800/7-1]
Ask authors/readers for more resources
We recently described a novel thiazide-sensitive electroneutral NaCI transport mechanism resulting from the parallel operation of the Cl-/HCO3- exchanger pendrin and the Na+-driven Cl-/2HCO(3)(-) exchanger (NDCBE) in beta-intercalated cells of the collecting duct. Although a role for pendrin in maintaining Na+ balance, intravascular volume, and BP is well supported, there is no in vivo evidence for the role of NDCBE in maintaining Na+ balance. Here, we show that deletion of NDCBE in mice caused only subtle perturbations of Na homeostasis and provide evidence that the Na+/Cl- cotransporter (NCC) compensated for the inactivation of NDCBE. To unmaskthe role of NDCBE, we generated Ndcbe/Ncdclouble-knockout (dKO) mice. On a normal salt diet, dKO and single-knockout mice exhibited similar activation of the renin-angiotensin-aldosterone system, whereas only dKO mice displayed a lower blood K concentration. Furthermore, dKO mice displayed upregulation of the epithelial sodium channel (ENaC) and the Ca2+-activated K+ channel BKCa. During NaCI depletion, only dKO mice developed marked intravascular volume contraction, despite dramatically increased renin activity. Notably, the increase in aldosterone levels expected on NaCI depletion was attenuated in dKO mice, and single-knockout and dKO mice had similar blood K+ concentrations under this condition. In conclusion, NDCBE is necessary for maintaining sodium balance and intravascular volume during salt depletion or NCC inactivation in mice. Furthermore, NDCBE has an important role in the prevention of hypokalemia. Because NCC and NDCBE are both thiazide targets, the combined inhibition of NCC and the NDCBE/pendrin system may explain thiazide-induced hypokalemia in some patients.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available