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Calcium Absorption Across Epithelia

Department of Physiology, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, Nijmegen, The Netherlands; and Department of Physiology, Campus Gasthuisberg, KU Leuven, Belgium

Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ balance, the kidney must excrete the same amount of Ca²⁺ that the small intestine absorbs. This is accomplished by a combination of filtration of Ca²⁺ across the glomeruli and subsequent reabsorption of the filtered Ca²⁺ along the renal tubules. Bone turnover is a continuous process involving both resorption of existing bone and deposition of new bone. The above-mentioned Ca²⁺ fluxes are stimulated by the synergistic actions of active vitamin D (1,25-dihydroxyvitamin D₃) and parathyroid hormone. Until recently, the mechanism by which Ca²⁺ enter the absorptive epithelia was unknown. A major breakthrough in completing the molecular details of these pathways was the identification of the epithelial Ca²⁺ channel family consisting of two members: TRPV5 and TRPV6. Functional analysis indicated that these Ca²⁺ channels constitute the rate-limiting step in Ca²⁺-transporting epithelia. They form the prime target for hormonal control of the active Ca²⁺ flux from the intestinal lumen or urine space to the blood compartment. This review describes the characteristics of epithelial Ca²⁺ transport in general and highlights in particular the distinctive features and the physiological relevance of the new epithelial Ca²⁺ channels accumulating in a comprehensive model for epithelial Ca²⁺ absorption.

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