Molecular mechanism of active Ca2+ reabsorption in the distal nephron

Annu Rev Physiol. 2002;64:529-49. doi: 10.1146/annurev.physiol.64.081501.155921.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calbindin 1
  • Calbindins
  • Calcium / metabolism*
  • Calcium Channels / metabolism
  • Humans
  • Kidney Tubules, Distal / metabolism
  • Nephrons / metabolism*
  • S100 Calcium Binding Protein G / metabolism
  • TRPV Cation Channels

Substances

  • CALB1 protein, human
  • Calbindin 1
  • Calbindins
  • Calcium Channels
  • S100 Calcium Binding Protein G
  • TRPV Cation Channels
  • TRPV5 protein, human
  • TRPV6 channel
  • Calcium