Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012 Jan;64(1):1-15.
doi: 10.1124/pr.111.005009. Epub 2011 Nov 16.

International Union of Basic and Clinical Pharmacology. LXXXV: calcium-activated chloride channels

Fen Huang  1 , Xiuming Wong, Lily Y Jan
Affiliations
Review

International Union of Basic and Clinical Pharmacology. LXXXV: calcium-activated chloride channels

Fen Huang et al. Pharmacol Rev. 2012 Jan.

Abstract

Calcium-activated chloride channels (CaCCs) are widely expressed in various tissues and implicated in physiological processes such as sensory transduction, epithelial secretion, and smooth muscle contraction. Transmembrane proteins with unknown function 16 (TMEM16A) has recently been identified as a major component of CaCCs. Detailed molecular analysis of TMEM16A will be needed to understand its structure-function relationships. The role this channel plays in physiological systems remains to be established and is currently a subject of intense investigation.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
Examples of classic CaCCs recorded in X. laevis oocytes and mammalian cells. A, CaCC in X. laevis oocyte. The patches were clamped from a holding potential of 0 mV to potentials between 140 and −100 mV for 1 s, followed by a 500-ms pulse to −100 mV (Qu and Hartzell, 2000). B, CaCC recorded in rat pulmonary artery (PA) smooth muscle cells, representative current tracings recorded in the absence (Control) and presence of 100 μM NFA, voltage-dependent currents were evoked by 1-s step depolarization from a holding potential of −50 mV to +70 mV, followed by 1-s return steps to −80 mV (Greenwood et al., 2001). C, CaCC recorded in cultured rat dorsal root ganglia neurons activated by a depolarizing prepulse (Mayer, 1985). D, CaCC recorded in ICCs. ICCs were depolarized from −80 to +30 mV in 10-mV increments from a holding potential of −80 mV, and ECl− was adjusted to 0 mV (Zhu et al., 2009).
Fig. 2.
Fig. 2.
Functional correlation between CaCC in native cells and TMEM16 family members. A, CaCC in submandibular salivary gland acinar cells is abolished in TMEM16A knock out mouse (Romanenko et al., 2010). B, CaCC in pulmonary arterial smooth muscle cells is greatly reduced by TMEM16A siRNA (Manoury et al., 2010). C, Slow wave activity in gastrointestinal muscles is abolished in TMEM16A knock out mouse (Hwang et al., 2009). D, CaCC is absent in the TMEM16B knockout mouse olfactory sensory neurons (Billig et al., 2011).
Fig. 3.
Fig. 3.
Proposed topology and functional domains of TMEM16A.
Fig. 4.
Fig. 4.
Phylogenetic analysis of 10 members of mouse TMEM16 proteins.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Agnel M, Vermat T, Culouscou JM. (1999) Identification of three novel members of the calcium-dependent chloride channel (CaCC) family predominantly expressed in the digestive tract and trachea. FEBS Lett 455:295–301 - PubMed
    1. Al-Jumaily M, Kozlenkov A, Mechaly I, Fichard A, Matha V, Scamps F, Valmier J, Carroll P. (2007) Expression of three distinct families of calcium-activated chloride channel genes in the mouse dorsal root ganglion. Neurosci Bull 23:293–299 - PMC - PubMed
    1. al-Nakkash L, Cotton CU. (1997) Bovine pancreatic duct cells express cAMP- and Ca2+-activated apical membrane Cl− conductances. Am J Physiol 273:G204–G216 - PubMed
    1. Anderson MP, Welsh MJ. (1991) Calcium and cAMP activate different chloride channels in the apical membrane of normal and cystic fibrosis epithelia. Proc Natl Acad Sci USA 88:6003–6007 - PMC - PubMed
    1. André S, Boukhaddaoui H, Campo B, Al-Jumaily M, Mayeux V, Greuet D, Valmier J, Scamps F. (2003) Axotomy-induced expression of calcium-activated chloride current in subpopulations of mouse dorsal root ganglion neurons. J Neurophysiol 90:3764–3773 - PubMed

Publication types

MeSH terms