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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Proximal renal tubular acidosis in TASK2 K+ channel-deficient mice reveals a mechanism for stabilizing bicarbonate transport.
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Proximal renal tubular acidosis in TASK2 K+ channel-deficient mice reveals a mechanism for stabilizing bicarbonate transport.

机译:TASK2 K +通道缺陷型小鼠的近端肾小管酸中毒揭示了稳定碳酸氢根转运的机制。

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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 HCO(3)(-) transport. In control inulin clearance measurements, task2 -/- mice showed normal NaCl and water excretion. During i.v. NaHCO(3) perfusion, however, renal Na(+) and water reabsorption capacity was reduced in -/- animals. In conscious task2 -/- mice, blood pH, HCO(3)(-) concentration, and systemic base excess were reduced but urinary pH and HCO(3)(-) were increased. These data suggest that task2 -/- mice exhibit metabolic acidosis caused by renal loss of HCO(3)(-). Both in vitro and in vivo resultsdemonstrate the specific coupling of TASK2 activity to HCO(3)(-) 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.
机译:酸和体积敏感的TASK2 K(+)通道在肾近端小管和乳头状集合管中强烈表达。这项研究旨在通过使用task2-/-小鼠模型研究TASK2在肾碳酸氢盐重吸收中的作用。回交到C57BL6后,task2-/-小鼠的围产期死亡率增加,成年后体重和动脉血压下降。近端肾小管细胞的膜片钳实验表明,TASK2在HCO(3)(-)转运过程中被激活。在对照菊粉清除率测量中,任务2-/-小鼠显示正常的NaCl和水排泄。在i.v. NaHCO(3)灌注,但是,-/-动物的肾Na(+)和水重吸收能力降低。在有意识的任务2-/-小鼠中,血液pH值,HCO(3)(-)浓度和全身性碱过量减少,但尿液pH和HCO(3)(-)增加。这些数据表明task2-/-小鼠表现出由HCO(3)(-)引起的肾脏丢失引起的代谢性酸中毒。体外和体内结果都证明TASK2活性与HCO(3)(-)的运输通过外部碱化的特定耦合。 task2基因失活在小鼠中的后果让人想起在人类近端肾小管酸中毒综合征中发现的临床表现。

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