Hoenderop Joost G J, Nilius Bernd, Bindels René J M
Department of Physiology, Nijmegen Center for Moecular Life Sciences, University Medical Center Nijmegen, The Netherlands.
Physiol Rev. 2005 Jan;85(1):373-422. doi: 10.1152/physrev.00003.2004.
Ca(2+) is an essential ion in all organisms, where it plays a crucial role in processes ranging from the formation and maintenance of the skeleton to the temporal and spatial regulation of neuronal function. The Ca(2+) balance is maintained by the concerted action of three organ systems, including the gastrointestinal tract, bone, and kidney. An adult ingests on average 1 g Ca(2+) daily from which 0.35 g is absorbed in the small intestine by a mechanism that is controlled primarily by the calciotropic hormones. To maintain the Ca(2+) balance, the kidney must excrete the same amount of Ca(2+) that the small intestine absorbs. This is accomplished by a combination of filtration of Ca(2+) across the glomeruli and subsequent reabsorption of the filtered Ca(2+) along the renal tubules. Bone turnover is a continuous process involving both resorption of existing bone and deposition of new bone. The above-mentioned Ca(2+) fluxes are stimulated by the synergistic actions of active vitamin D (1,25-dihydroxyvitamin D(3)) and parathyroid hormone. Until recently, the mechanism by which Ca(2+) enter the absorptive epithelia was unknown. A major breakthrough in completing the molecular details of these pathways was the identification of the epithelial Ca(2+) channel family consisting of two members: TRPV5 and TRPV6. Functional analysis indicated that these Ca(2+) channels constitute the rate-limiting step in Ca(2+)-transporting epithelia. They form the prime target for hormonal control of the active Ca(2+) flux from the intestinal lumen or urine space to the blood compartment. This review describes the characteristics of epithelial Ca(2+) transport in general and highlights in particular the distinctive features and the physiological relevance of the new epithelial Ca(2+) channels accumulating in a comprehensive model for epithelial Ca(2+) absorption.
钙离子是所有生物体中的一种必需离子，它在从骨骼形成和维持到神经元功能的时空调节等过程中发挥着关键作用。钙离子平衡由三个器官系统（包括胃肠道、骨骼和肾脏）的协同作用维持。成年人平均每天摄入1克钙离子，其中0.35克在小肠中通过主要受钙调节激素控制的机制被吸收。为维持钙离子平衡，肾脏必须排泄与小肠吸收量相同的钙离子。这是通过钙离子在肾小球的滤过以及随后沿肾小管对滤过钙离子的重吸收来实现的。骨转换是一个持续的过程，涉及现有骨的吸收和新骨的沉积。上述钙离子通量受到活性维生素D（1,25 - 二羟基维生素D3）和甲状旁腺激素的协同作用刺激。直到最近，钙离子进入吸收上皮细胞的机制仍不清楚。在完善这些途径的分子细节方面的一个重大突破是鉴定出由两个成员组成的上皮钙离子通道家族：TRPV5和TRPV6。功能分析表明，这些钙离子通道构成了钙离子转运上皮细胞中限速步骤。它们形成了从肠腔或尿液空间到血液 compartment 的活性钙离子通量激素控制的主要靶点。本综述描述了上皮钙离子转运的一般特征，并特别强调了新的上皮钙离子通道的独特特征及其在综合上皮钙离子吸收模型中的生理相关性。
