Active Ca2+ reabsorption in the connecting tubule
Active Ca2+ reabsorption in the connecting tubule
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DOI：
10.1007/s00424-008-0602-6
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发表时间：
2009-05-01
影响因子：
4.5
通讯作者：
Hoenderop, Joost G. J.
中科院分区：
文献类型：
--
作者：
Boros, Sandor;Bindels, Rene J. M.;Hoenderop, Joost G. J.
肾脏在维持体内钙（Ca 2+）平衡方面起着至关重要的作用。Ca 2+是所有生物体中必不可少的离子，并参与各种结构和功能过程。在哺乳动物中，活性肾小管Ca 2+重吸收仅限于肾单位的远端部分，即，晚远曲小管（DCT 2）和连接小管（CNT），其中约10-15%的总Ca 2+被重吸收。这种主动跨细胞转运的标志是瞬时受体电位香草酸5（TRPV 5）上皮钙通道，由一系列事件调节，并由激素介导，包括1，25-二羟基维生素D-3，甲状旁腺激素和雌激素。新的分子机制已被确定，如klotho和组织激肽释放酶对TRPV 5在顶膜丰度的直接调节作用。这些新发现的机制为肾性钙消耗的治疗提供了潜在的药理学靶点。这篇综述讨论了三个基本的分子步骤的活性钙重吸收的DCT/CNT段的肾单位，包括顶端进入，细胞质运输，和基底外侧的钙离子的挤出。此外，最近确定的机制，管理这一积极的Ca 2+运输通过DCT 2/CNT上皮细胞的概述。
The kidney plays a crucial role in the maintenance of the body calcium (Ca2+) balance. Ca2+ is an essential ion in all organisms and participates in a large variety of structural and functional processes. In mammals, active tubular Ca2+ reabsorption is restricted to the distal part of the nephron, i.e., the late distal convoluted (DCT2) and the connecting tubules (CNT), where approximately 10-15% of the total Ca2+ is reabsorbed. This active transcellular transport is hallmarked by the transient receptor potential vanilloid 5 (TRPV5) epithelial Ca2+ channel, regulated by an array of events, and mediated by hormones, including 1,25-dihydroxyvitamin D-3, parathyroid hormone, and estrogen. Novel molecular mechanisms have been identified, such as the direct regulatory effects of klotho and tissue kallikrein on the abundance of TRPV5 at the apical membrane. The newly discovered mechanisms could provide potential pharmacological targets in the therapy of renal Ca2+ wasting. This review discusses the three basic molecular steps of active Ca2+ reabsorption in the DCT/CNT segments of the nephron, including apical entry, cytoplasmic transport, and basolateral extrusion of Ca2+. In addition, an overview of the recently identified mechanisms governing this active Ca2+ transport through the DCT2/CNT epithelial cells will be presented.