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Molecular identification of the apical Ca2+ channel in 1, 25-dihydroxyvitamin D3-responsive epithelia Hoenderop JG; van der Kemp AW; Hartog A; van de Graaf SF; van Os CH; Willems PH; Bindels RJJ Biol Chem 1999[Mar]; 274 (13): 8375-8In 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 D3-dependent calbindin-D28K. 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 D3-dependent active transepithelial Ca2+ transport.|Amino Acid Sequence[MESH]|Animals[MESH]|Biological Transport[MESH]|Calbindins[MESH]|Calcitriol/*pharmacology[MESH]|Calcium Channels/analysis/*chemistry/genetics[MESH]|Calcium/metabolism[MESH]|Cells, Cultured[MESH]|Cloning, Molecular[MESH]|Epithelial Cells/*metabolism[MESH]|Immunohistochemistry[MESH]|Kidney Tubules/*metabolism[MESH]|Molecular Sequence Data[MESH]|RNA, Messenger/metabolism[MESH]|Rabbits[MESH]|S100 Calcium Binding Protein G/metabolism[MESH]|Sequence Alignment[MESH]|Sequence Analysis, DNA[MESH]|Substrate Specificity[MESH]|TRPV Cation Channels[MESH] |
