Calcium Absorption Across Epithelia

Abstract

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.