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Proximal Renal Tubular Acidosis in TASK2 K+ Channel-Deficient Mice Reveals a Mechanism for Stabilizing Bicarbonate Transport
Richard Warth, Hervé Barrière, Pierre Meneton, May Bloch, Jörg Thomas, Michel Tauc, Dirk Heitzmann, Elisa Romeo, François Verrey, Raymond Mengual, Nicolas Guy, Saïd Bendahhou, Florian Lesage, Philippe Poujeol, Jacques Barhanin and Lily Y. Jan
Proceedings of the National Academy of Sciences of the United States of America
Vol. 101, No. 21 (May 25, 2004), pp. 8215-8220
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/3372477
Page Count: 6
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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.
Proceedings of the National Academy of Sciences of the United States of America © 2004 National Academy of Sciences