Sensing mechanisms involved in Ca2+ and Mg2+ homeostasis Silvia Ferrè, Joost G.J. Hoenderop, René J.M. Bindels  Kidney International  Volume 82, Issue 11, Pages 1157-1166 (December 2012) DOI: 10.1038/ki.2012.179 Copyright © 2012 International Society of Nephrology Terms and Conditions

Figure 1 Schematic representation of Ca2+ and Mg2+ homeostasis. Dashed arrow: paracellular transport; solid arrow: transcellular transport. CaSR, calcium-sensing receptor; CLDN16, claudin-16; CLDN19, claudin-19; CNT, connecting tubule; DCT, distal convoluted tubule; PTH, parathyroid hormone; PT, proximal tubule; TAL, thick ascending limb of Henle; TRPM6, transient receptor potential melastatin 6; TRPV4, transient receptor potential vanilloid 4; TRPV5, transient receptor potential vanilloid 5; TRPV6, transient receptor potential vanilloid 6. Kidney International 2012 82, 1157-1166DOI: (10.1038/ki.2012.179) Copyright © 2012 International Society of Nephrology Terms and Conditions

Figure 2 Key regulators of PTH expression and PTH secretion in a parathyroid gland cell model. Fluctuations in plasma Ca2+ and Mg2+ levels modulate PTH release from secretory granules via CaSR-mediated signaling. In hypocalcemic conditions, 1,25(OH)2D3 can bind its receptor VDR and act as negative feedback mechanism on PTH and CaSR promoters. When hyperphosphatemia occurs, FGF23 binds to the Klotho/FGFR1 complex and inhibits the PTH expression and release. More recently, it has been hypothesized that the NaK-ATPase/Klotho complex can regulate PTH secretion. CaSR, calcium-sensing receptor; 1,25(OH)2D3, 1,25-dihydroxyvitamin D3; FGFR1, FGF receptor 1; FGF23, fibroblast growth factor 23; NaK-ATPase, Na+–K+ ATPase pump; PTH, parathyroid hormone; VDR, vitamin D receptor. Kidney International 2012 82, 1157-1166DOI: (10.1038/ki.2012.179) Copyright © 2012 International Society of Nephrology Terms and Conditions