期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：21
页码：8215-8220
DOI：10.1073/pnas.0400081101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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 [IMG]f1.gif" BORDER="0"> 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, [IMG]f1.gif" BORDER="0"> concentration, and systemic base excess were reduced but urinary pH and [IMG]f1.gif" BORDER="0"> were increased. These data suggest that task2 -/- mice exhibit metabolic acidosis caused by renal loss of [IMG]f1.gif" BORDER="0">. Both in vitro and in vivo results demonstrate the specific coupling of TASK2 activity to [IMG]f1.gif" BORDER="0"> 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.
