NHE8 attenuates Ca influx into NRK cells and the proximal tubule epithelium.

To garner insights into the renal regulation of Ca homeostasis, we performed an mRNA microarray on kidneys from mice treated with the Ca-sensing receptor (CaSR) agonist cinacalcet. This revealed decreased gene expression of Na/H exchanger isoform 8 (NHE8) in response to CaSR activation. These results were confirmed by quantitative real-time PCR.

Carbonic anhydrase II binds to and increases the activity of the epithelial sodium-proton exchanger, NHE3.

Two-thirds of sodium filtered by the renal glomerulus is reabsorbed from the proximal tubule via a sodium/proton exchanger isoform 3 (NHE3)-dependent mechanism. Since sodium and bicarbonate reabsorption are coupled, we postulated that the molecules involved in their reabsorption [NHE3 and carbonic anhydrase II (CAII)] might physically and functionally interact. Consistent with this, CAII and NHE3 were closely associated in a renal proximal tubular cell culture model as revealed by a proximity ligation assay.