Molecular Identification of the Apical Ca2+Channel in 1,25-Dihydroxyvitamin D3-responsive Epithelia
Journal of Biological Chemistry
In mammals, the extracellular calcium concentration is maintained within a narrow range despite large variations in daily dietary input and body demand. The small intestine and kidney constitute the influx pathways into the extracellular Ca 2؉ pool and, therefore, play a primary role in Ca 2؉ homeostasis. We identified an apical Ca 2؉ influx channel, which is expressed in proximal small intestine, the distal part of the nephron and placenta. This novel epithelial Ca 2؉ channel (ECaC) of 730
... l (ECaC) of 730 amino acids contains six putative membranespanning domains with an additional hydrophobic stretch predicted to be the pore region. ECaC resembles the recently cloned capsaicin receptor and the transient receptor potential-related ion channels with respect to its predicted topology but shares less than 30% sequence homology with these channels. In kidney, ECaC is abundantly present in the apical membrane of Ca 2؉ transporting cells and colocalizes with 1,25-dihydroxyvitamin D 3 -dependent calbindin-D 28K . ECaC expression in Xenopus oocytes confers Ca 2؉ influx with properties identical to those observed in distal renal cells. Thus, ECaC has the expected properties for being the gatekeeper of 1,25-dihydroxyvitamin D 3 -dependent active transepithelial Ca 2؉ transport.