Proximal renal tubular acidosis in TASK2 K+ channel-deficient mice reveals a mechanism for stabilizing bicarbonate transport.
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.
Warth
Richard
R
Institute of Physiology, Universitätsstrasse 31, 93053 Regensburg, Germany.
Barrière
Hervé
H
Meneton
Pierre
P
Bloch
May
M
Thomas
Jörg
J
Tauc
Michel
M
Heitzmann
Dirk
D
Romeo
Elisa
E
Verrey
François
F
Mengual
Raymond
R
Guy
Nicolas
N
Bendahhou
Saïd
S
Lesage
Florian
F
Poujeol
Philippe
P
Barhanin
Jacques
J
D000141:Acidosis, Renal Tubular / Q000097:blood / Q000235:genetics* / Q000503:physiopathology* / Q000652:urine; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism* / Q000652:urine; D001692:Biological Transport; D002478:Cells, Cultured; D003243:Consciousness; D017353:Gene Deletion; D007668:Kidney / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D015221:Potassium Channels / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain; D012964:Sodium / Q000652:urine; D014556:Urine / Q000737:chemistry
D001639:Bicarbonates; C498739:Kcnk5 protein, mouse; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D012964:Sodium