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lüll Molecular mechanism of active Ca2+ reabsorption in the distal nephron Hoenderop JG; Nilius B; Bindels RJAnnu Rev Physiol 2002[]; 64 (ä): 529-49The identification of the epithelial Ca(2+) channel (ECaC) complements the group of Ca(2+) transport proteins including calbindin-D28K, Na(+)/Ca(2+) exchanger and plasma membrane Ca(2+)-ATPase, which are co-expressed in 1,25(OH)2D3- responsive nephron segments. ECaC constitutes the rate-limiting apical entry step in the process of active transcellular Ca(2+) transport and belongs to a superfamily of Ca(2+) channels that includes the vanilloid receptor and transient receptor potential channels. This new Ca(2+) channel consists of six transmembrane-spanning domains, including a pore-forming hydrophobic stretch between domain 5 and 6. The C- and N-terminal tails contain several conserved regulatory sites, implying that the channel function is modulated by regulatory proteins. The distinctive functional properties of ECaC include a constitutively activated Ca(2+) permeability, a high selectivity for Ca(2+), hyperpolarization-stimulated and Ca(2+)-dependent feedback regulation of channel activity, and 1,25(OH)2D3-induced gene activation. This review covers the distinctive properties of this new highly Ca(2+)-selective channel and highlights the implications for active transcellular Ca(2+) reabsorption in health and disease.|Animals[MESH]|Calbindin 1[MESH]|Calbindins[MESH]|Calcium Channels/metabolism[MESH]|Calcium/*metabolism[MESH]|Humans[MESH]|Kidney Tubules, Distal/metabolism[MESH]|Nephrons/*metabolism[MESH]|S100 Calcium Binding Protein G/metabolism[MESH]|TRPV Cation Channels[MESH] |