Molecular mechanism of active Ca2+ reabsorption in the distal nephron.
The 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.
Hoenderop
Joost G J
JG
Department of Cell Physiology, Institute of Cellular Signalling, University Medical Centre Nijmegen, The Netherlands.
Nilius
Bernd
B
Bindels
Rene J M
RJ
D000818:Animals; D064092:Calbindin 1; D064026:Calbindins; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D006801:Humans; D007686:Kidney Tubules, Distal / Q000378:metabolism; D009399:Nephrons / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D050916:TRPV Cation Channels
C576498:CALB1 protein, human; D064092:Calbindin 1; D064026:Calbindins; D015220:Calcium Channels; D064030:S100 Calcium Binding Protein G; D050916:TRPV Cation Channels; C492239:TRPV5 protein, human; C120776:TRPV6 channel; D002118:Calcium