Objective: 

The calcium-sensing receptor (CaSR) is a G-protein coupled receptor and tightly involved in the maintenance of calcium homeostasis. It is differentially expressed along the nephron and in literature several functions are discussed. In the collecting duct it is localized in the luminal membrane and supposed to regulate epithelial water permeability and acid secretion to prevent stone formation. We investigated the functional expression of CaSR in M1 cells.

Methods: 

We measured the effect of different extracellular calcium concentrations by fura-2 fluorescence. In the absence and presence of calindol, a CaSR sensitizer, we established concentration response relations. In addition, we did Ussing chamber experiments to determine the effect of luminal calcium and calindol on electrogenic ion transport across confluent M1 cell monolayers.

Results: 

The increase in extracellular calcium elicited a change in intracellular Ca₂₊ in a concentration depended manner with an EC₅₀ of 2.7 mmol/l. 1 mmol/l calindol induced a left shift in the concentration dependency to an EC₅₀ of 1.9 mmol/l calcium. 3mmol/l calindol shifted EC₅₀ to 1.4 mmol/l, respectively. The calindol concentration response at a constant calcium of 1 mmol/l resulted in an EC₅₀ of 5.7 mmol/l. In Ussing chamber experiments luminal application of 5 mmol/l CaCl₂ as well as 10 mmol/l calindol induced a small decrease in short-circuit current by 1.9 ± 0.6 mA/cm² (n=9) and 2.7 ± 1.3 mA/cm² (n=6), respectively.

Conclusion: 

M1 cells functionally express the CaSR and might serve in further investigations as a tool to understand the function of the CaSR in collecting duct principal cells.