Penton, David and Czogalla, Jan and Wengi, Agnieszka and Himmerkus, Nina and Loffing-Cueni, Dominique and Carrel, Monique and Rajaram, Renuga Devi and Staub, Olivier and Bleich, Markus and Schweda, Frank and Loffing, Johannes (2016) Extracellular K+ rapidly controls NaCl cotransporter phosphorylation in the native distal convoluted tubule by Cl--dependent and independent mechanisms. JOURNAL OF PHYSIOLOGY-LONDON, 594 (21). pp. 6319-6331. ISSN 0022-3751, 1469-7793
Full text not available from this repository. (Request a copy)Abstract
A high dietary potassium (K+) intake causes a rapid dephosphorylation, and hence inactivation, of the thiazide-sensitive NaCl cotransporter (NCC) in the renal distal convoluted tubule (DCT). Based on experiments in heterologous expression systems, it was proposed that changes in extracellular K+ concentration ([K+](ex)) modulate NCC phosphorylation via a Cl--dependent modulation of the with no lysine (K) kinases (WNK)-STE20/SPS-1-44 related proline-alanine-rich protein kinase (SPAK)/oxidative stress-related kinase (OSR1) kinase pathway. We used the isolated perfused mouse kidney technique and ex vivo preparations of mouse kidney slices to test the physiological relevance of this model on native DCT. We demonstrate that NCC phosphorylation inversely correlates with [K+](ex), with the most prominent effects occurring around physiological plasma [K+]. Cellular Cl- conductances and the kinases SPAK/OSR1 are involved in the phosphorylation of NCC under low [K+](ex). However, NCC dephosphorylation triggered by high [K+](ex) is neither blocked by removing extracellular Cl-, nor by the Cl- channel blocker 4,4-diisothiocyano-2,2-stilbenedisulphonic acid. The response to [K+](ex) on a low extracellular chloride concentration is also independent of significant changes in SPAK/OSR1 phosphorylation. Thus, in the native DCT, [K+](ex) directly and rapidly controls NCC phosphorylation by Cl--dependent and independent pathways that involve the kinases SPAK/OSR1 and a yet unidentified additional signalling mechanism.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SODIUM-CHLORIDE COTRANSPORTER; BLOOD-PRESSURE; POTASSIUM EXCRETION; BARTTERS-SYNDROME; URINARY SODIUM; NA+; EXPRESSION; NCC; HYPERTENSION; MICE; potassium; sodium transport; signal transduction |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Frank Schweda |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Apr 2019 08:57 |
| Last Modified: | 24 Apr 2019 08:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4033 |
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