Molecular identification of the apical Ca2+ channel in 1,25-dihydroxyvitamin D-3-responsive epithelia

J. G. Hoenderop, A. W. van der Kemp, A. Hartog, S. F. van de Graaf, C. H. van Os, P. H. Willems, R. J. Bindels

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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 Ca2+ pool and, therefore, play a primary role in Ca2+ homeostasis, We identified an apical Ca2+ influx channel, which is expressed in proximal small intestine, the distal part of the nephron and placenta. This novel epithelial Ca2+ channel (ECaC) of 730 amino acids contains six putative membrane-spanning 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 Ca2+ transporting cells and colocalizes with 1,25-dihydroxyvitamin D-3-dependent calbindin-D-28K. ECaC expression in Xenopus oocytes confers Ca2+ 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 Ca2+ transport
Original languageEnglish
Pages (from-to)8375-8378
JournalJournal of biological chemistry
Issue number13
Publication statusPublished - 1999

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