Department of Physiology (286), Radboud University Nijmegen Medical Centre (RUNMC), P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Clin J Am Soc Nephrol. 2011 Aug;6(8):2076-82. doi: 10.2215/CJN.00480111. Epub 2011 Jul 22.
The tight control of blood Ca2+ levels within a narrow range is essential for the performance of vital physiologic functions. Muscle contraction, neuronal excitation, and intracellular signaling processes acquisitively require Ca2+. It is the concerted action of intestine, bone, and kidney that controls the Ca2+ balance through the regulation of intestinal absorption, bone (de)mineralization, and renal excretion of Ca2+, respectively. Along the nephron, fine-tuning of blood Ca2+ levels takes place by Ca2+ reabsorption. The calciotropic hormones regulate Ca2+ transport processes, leading to whole-body Ca2+ homeostasis and, importantly, preserving a constant Ca2+ concentration in the blood. Defects in renal Ca2+ handling can lead to hypercalciuria, consecutive kidney stone formation, and obstructive nephropathy. Here we give an overview of the key players involved in normal Ca2+ management and describe the in-depth investigations on a renal hypercalciuric model of disease, the Trpv5 knockout mouse, which naturally displays molecular adaptations that prevent Ca2+ precipitation in the kidney.
血钙水平的严格控制在狭窄范围内对于重要生理功能的发挥至关重要。肌肉收缩、神经元兴奋和细胞内信号转导过程都需要 Ca2+。肠道、骨骼和肾脏通过调节肠道吸收、骨骼（脱）矿化以及肾脏对 Ca2+的排泄，协同作用来控制 Ca2+平衡。在肾单位中，通过 Ca2+重吸收来精细调节血钙水平。钙调节激素调节 Ca2+转运过程，导致全身 Ca2+稳态，重要的是，保持血液中 Ca2+浓度的恒定。肾脏对 Ca2+的处理缺陷可导致高钙尿症、随后的肾结石形成和梗阻性肾病。在这里，我们概述了参与正常 Ca2+管理的关键因素，并描述了对肾脏高钙尿症疾病模型，即 TRPV5 基因敲除小鼠的深入研究，该模型自然表现出分子适应性，可防止 Ca2+在肾脏中沉淀。
