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Proximal renal tubular acidosis in TASK2 K+ channel-deficient mice reveals a mechanism for stabilizing bicarbonate transport.
Proximal renal tubular acidosis in TASK2 K+ channel-deficient mice reveals a mechanism for stabilizing bicarbonate transport.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2004 May 25; Vol. 101 (21), pp. 8215-20. Date of Electronic Publication: 2004 May 12. - Publication Year :
- 2004
-
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.
- Subjects :
- Acidosis, Renal Tubular blood
Acidosis, Renal Tubular urine
Animals
Bicarbonates urine
Biological Transport
Cells, Cultured
Consciousness
Gene Deletion
Kidney physiopathology
Male
Mice
Mice, Knockout
Models, Biological
Potassium Channels genetics
Potassium Channels metabolism
Sodium urine
Urine chemistry
Acidosis, Renal Tubular genetics
Acidosis, Renal Tubular physiopathology
Bicarbonates metabolism
Potassium Channels deficiency
Potassium Channels, Tandem Pore Domain
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 101
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 15141089
- Full Text :
- https://doi.org/10.1073/pnas.0400081101