Warth, Richard and Barriere, Herve and Meneton, Pierre and Bloch, May and Thomas, Joerg and Tauc, Michel and Heitzmann, Dirk and Romeo, Elisa and Verrey, Francois and Mengual, Raymond and Guy, Nicolas and Bendahhou, Said and Lesage, Florian and Poujeol, Philippe and Barhanin, Jaques (2004) Proximal renal tubular acidosis in TASK2 K+ channel-deficient mice reveals a mechanism for stabilizing bicarbonate transport. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 101 (21). pp. 8215-8220. ISSN 0027-8424,
Full text not available from this repository. (Request a copy)Abstract
The acid- and volume-sensitive TASK2 K+ channel is strongly expressed in renal proximal tubules and papillary collecting ducts. This study was aimed at investigating the role of TASK2 in renal bicarbonate reabsorption by using the task2 -/- mouse as a model. After backcross to C57BL6, task2 -/- mice showed an increased perinatal mortality and, in adulthood, a reduced body weight and arterial blood pressure. Patch-clamp experiments on proximal tubular cells indicated that TASK2 was activated during HCO3- transport. In control inulin clearance measurements, task2 -/- mice showed normal NaCl and water excretion. During i.v. NaHCO3 perfusion, however, renal Na+ and water reabsorption capacity was reduced in -/- animals. In conscious task2 -/- mice, blood pH, HCO3- concentration, and systemic base excess were reduced but urinary pH and HCO3- were increased. These data suggest that task2 -/- mice exhibit metabolic acidosis caused by renal loss of HCO3-. Both in vitro and in vivo results demonstrate the specific coupling of TASK2 activity to HCO3- transport through external alkalinization. The consequences of the task2 gene inactivation in mice are reminiscent of the clinical manifestations seen in human proximal renal tubular acidosis syndrome.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | POTASSIUM CHANNELS; HUMAN KIDNEY; BASOLATERAL MEMBRANE; CONVOLUTED TUBULE; BARTTERS-SYNDROME; VOLUME REGULATION; MOUSE DEVELOPMENT; APICAL MEMBRANES; EXPRESSION; CONDUCTANCE; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Richard Warth |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Jul 2021 06:18 |
| Last Modified: | 20 Jul 2021 06:18 |
| URI: | https://pred.uni-regensburg.de/id/eprint/37636 |
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