Molecular basis of epithelial Ca²⁺ and Mg²⁺ transport: insights from the TRP channel family

Abstract

Maintenance of plasma Ca 2+ and Mg 2+ levels is of vital importance for many physiological functions. This is achieved via a coordinated interplay between the intestine, bone and kidney by amending the rate of absorption, storage and excretion, respectively. Discovery of the transient receptor potential (TRP) family identified several new ion channels acting as gatekeepers of Ca 2+ and Mg 2+ transport in these epithelia, greatly increasing our understanding of the molecular processes that facilitate the movement of these minerals. In the intestine, TRP channels contribute to the saturable active transcellular movement of divalent cations from the lumen into the enterocyte. Furthermore, in bone, TRPV channels play important roles by influencing the osteoclastic resorption process, thereby contributing importantly to overall bone mineral content. The divalent cation-permeable TRPV5 and TRPM6 channels are located in the renal distal convolution, the main site of active transcellular Ca 2+ and Mg 2+ transport. The channels are regulated by a multitude of factors and hormones that contribute importantly to keeping the systemic concentrations of Ca 2+ and Mg 2+ within normal limits. Dysregulation of either channel impacts the renal reabsorptive capacity for these cations. This review summarizes the current knowledge related to TRP channels in epithelial Ca 2+ and Mg 2+ transport.

Effect of Oestrogen on Altering the Serum and Urinary Levels of Calcium, Phosphate and Magnesium in Hysterectomised Women Compared to Natural Menopausal South Indian Women: A Case Control Study

“…Studies have shown that the absorption of calcium in small intestine takes place by a estrogen regulated metabolically driven active transcellular pathway and a saturable gradient dependent passive paracellular pathway across the intestinal cells [4], and generally the global calcium absorption in postmenopausal women is decreased more so in case of postmenopausal women with osteoporosis. Calcium absorption decreases in older age due to decrease in oestrogen, calcitriol and increase in end organ resistance to calcitriol.…”

Segmental transport of Ca2+and Mg2+along the gastrointestinal tract

“…The epithelial mineral channels, TRPV6 and TRPM6, form the gatekeepers of Ca 2ϩ and Mg 2ϩ absorption, respectively, along the gastrointestinal tract (10,29). In humans, TRPV6 is expressed predominantly in the stomach and duodenum, whereas TRPM6 is mainly expressed in the ileum and colon.…”

Epigenetic Regulation of MicroRNAs Controlling CLDN14 Expression as a Mechanism for Renal Calcium Handling

“…The predominant Ca ++ reabsorption sites are in the PT, the TALH, and the DCT. 11,12 Although the PT and TALH use the paracellular pathway to handle Ca ++ , 11 the DCT relies on a coordinated transcellular Ca ++ transport pathway based on the apically localized transient receptor potential channel V member 5 (TRPV5) and the basolaterally localized Na + /Ca ++ exchanger 1 (NCX1). 12 Because HDAC is a global regulator of gene expression, its renal effects could stem from different tubular segments.…”

“…11,12 Although the PT and TALH use the paracellular pathway to handle Ca ++ , 11 the DCT relies on a coordinated transcellular Ca ++ transport pathway based on the apically localized transient receptor potential channel V member 5 (TRPV5) and the basolaterally localized Na + /Ca ++ exchanger 1 (NCX1). 12 Because HDAC is a global regulator of gene expression, its renal effects could stem from different tubular segments. Here, with ex vivo tubule perfusion approaches and using animal models defective for TALH Ca ++ transport (CLDN14 knockout [KO] or furosemide-treated mice), we have conclusively shown that the TALH is the primary target segment of HDAC inhibition.…”