Intracellular Ca2+ and Cl- Channel Activation in Secretory Cells

Annu Rev Physiol. 2000;62:493-513. doi: 10.1146/annurev.physiol.62.1.493.


Molecular and functional evidence indicates that a variety of Ca(2+)-dependent chloride (Cl(Ca)) channels are involved in fluid secretion from secretory epithelial cells in different tissues and species. Most Cl(Ca) channels so far characterized have an I- permeability greater than Cl-, and most are sensitive to 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Whole-cell Cl(Ca) currents show outward rectification. Single-channel current voltage relationships are linear with conductances ranging from 2 to 30 pS. Some Cl(Ca) channels are blocked by Ca(2+)-calmodulin-dependent protein kinase (CAMKII) inhibitors. Others, such as the Cl(Ca) channels of parotid and submandibular acinar cells, appear to be directly regulated by Ca2+. In native cells, the Cl(Ca) channels are located on the apical plasma membrane and activated by localized mechanisms of Ca2+ release. This positioning allows the Cl(Ca) channel to respond specifically to localized Ca2+ signals that do not invade other regions of the cell. The Cl(Ca) follows the rising phase of the Ca2+ signal, but in the falling phase hysteresis occurs where the Cl(Ca) current decays more rapidly than the underlying Ca2+. The future elucidation of the identity and mechanisms of regulation of Cl(Ca) channels will be critical to our understanding of stimulus-secretion coupling.

Publication types

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

MeSH terms

  • Animals
  • Calcium Channels / metabolism*
  • Chloride Channels / metabolism*
  • Epithelial Cells / metabolism*
  • Humans
  • Intestinal Mucosa / metabolism*


  • Calcium Channels
  • Chloride Channels