Double Knockout of the Na + -Driven Cl − /HCO 3 − Exchanger and Na + /Cl − Cotransporter Induces Hypokalemia and Volume Depletion
Autor: | Régine Chambrey, Christian A. Hübner, Anne Sinning, Maximilien Jayat, Karen I. López-Cayuqueo, Stéphanie Baron, R. Todd Alexander, Nicolas Cornière, Juliette Hadchouel, Dominique Eladari, Nikita Radionov, Francesco Trepiccione |
---|---|
Přispěvatelé: | Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Centro de Estudios Científicos (CECs), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), University of Alberta, Centre National de la Recherche Scientifique (CNRS), Hadchouel, Juliette, Sinning, Anne, Radionov, Nikita, Trepiccione, Francesco, López Cayuqueo, Karen I, Jayat, Maximilien, Baron, Stéphanie, Cornière, Nicola, Alexander, R. Todd, Eladari, Dominique, Hübner, Christian A, Chambrey, Régine |
Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Epithelial sodium channel medicine.medical_specialty hypertension [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] diuretic 030232 urology & nephrology Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system In vivo Internal medicine medicine hypokalemia [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] Animals Chloride-Bicarbonate Antiporters Thiazide Mice Knockout Blood Volume biology Animal Chemistry Chloride-Bicarbonate Antiporter General Medicine Pendrin Hypokalemia diuretics Up-Regulation [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system Basic Research 030104 developmental biology Endocrinology Nephrology biology.protein medicine.symptom Cotransporter Homeostasis medicine.drug |
Zdroj: | Journal of the American Society of Nephrology Journal of the American Society of Nephrology, 2017, 28 (1), pp.130-139. ⟨10.1681/ASN.2015070734⟩ |
ISSN: | 1046-6673 1533-3450 |
Popis: | International audience; We recently described a novel thiazide-sensitive electroneutral NaCl transport mechanism resulting from the parallel operation of the Cl-/HCO3- exchanger pendrin and the Na+-driven Cl-/2HCO3- exchanger (NDCBE) in β-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 unmask the role of NDCBE, we generated Ndcbe/Ncc double-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 NaCl depletion, only dKO mice developed marked intravascular volume contraction, despite dramatically increased renin activity. Notably, the increase in aldosterone levels expected on NaCl 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. |
Databáze: | OpenAIRE |
Externí odkaz: |