New functional aspects of the extracellular calcium-sensing receptor

Curr Opin Nephrol Hypertens. 2014 Jul;23(4):352-60. doi: 10.1097/01.mnh.0000447016.21228.e0.


Purpose of review: Variations in extracellular calcium level have a large impact on kidney function. Most of the effects seen are attributed to the calcium-sensing receptor (CaSR), a widely expressed G-protein-coupled cell surface protein with an important function in bone mineral homeostasis. The purpose of this review is to recapitulate the novel functional aspects of CaSR.

Recent findings: Results from mouse models demonstrate important functions for CaSR in various tissues. In the kidney, the main role of CaSR is the regulation of calcium reabsorption in the thick ascending limb, independently of its role on parathyroid hormone secretion. CaSR modulates claudin 14, the gatekeeper of paracellular ion transport in the thick ascending limb that is associated with urinary calcium excretion. One intracellular signaling pathway by which CaSR alters tight junction permeability is the calcineurin-NFAT1c-microRNA-claudin14 axis.

Summary: The main function of CaSR in the kidney is the regulation of calcium excretion in the thick ascending limb, independently of parathyroid hormone. CaSR modulates paracellular cation transport by altering expression of the tight junction protein claudin 14. Still more work is needed to fully understand all functions of CaSR in the kidney. Alternative pathways of calcium 'sensing' in the kidney need to be investigated.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium / urine
  • Claudins / metabolism
  • Homeostasis
  • Humans
  • Hypercalcemia / congenital
  • Hypercalcemia / genetics
  • Hyperparathyroidism / genetics
  • Kidney / metabolism*
  • Mice
  • Models, Animal
  • Permeability
  • Receptors, Calcium-Sensing / genetics*
  • Receptors, Calcium-Sensing / metabolism*
  • Signal Transduction
  • Tight Junctions / metabolism*


  • Claudins
  • Receptors, Calcium-Sensing
  • Calcium
  • claudin 14

Supplementary concepts

  • Hypocalciuric hypercalcemia, familial, type 1