Proximal Renal Tubular Acidosis in TASK2 K+ Channel-Deficient Mice Reveals a Mechanism for Stabilizing Bicarbonate Transport

Proc Natl Acad Sci U S A. 2004 May 25;101(21):8215-20. doi: 10.1073/pnas.0400081101. Epub 2004 May 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis, Renal Tubular / blood
  • Acidosis, Renal Tubular / genetics*
  • Acidosis, Renal Tubular / physiopathology*
  • Acidosis, Renal Tubular / urine
  • Animals
  • Bicarbonates / metabolism*
  • Bicarbonates / urine
  • Biological Transport
  • Cells, Cultured
  • Consciousness
  • Gene Deletion
  • Kidney / physiopathology
  • Male
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Potassium Channels / deficiency*
  • Potassium Channels / genetics
  • Potassium Channels / metabolism
  • Potassium Channels, Tandem Pore Domain*
  • Sodium / urine
  • Urine / chemistry

Substances

  • Bicarbonates
  • Kcnk5 protein, mouse
  • Potassium Channels
  • Potassium Channels, Tandem Pore Domain
  • Sodium