Calcium activated chloride channel C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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Chloride channels activated by intracellular calcium (CaCC) are widely expressed in excitable and non-excitable cells where they perform diverse functions [8]. The molecular nature of CaCC has been uncertain with both CLCA, TWEETY and BEST genes having been considered as likely candidates [5,9,12]. It is now accepted that CLCA expression products are unlikely to form channels per se and probably function as cell adhesion proteins, or are secreted [16]. Similarly, TWEETY gene products do not recapictulate the properties of endogenous CaCC. The bestrophins encoded by genes BEST1-4 have a topology more consistent with ion channels [9] and form chloride channels that are activated by physiological concentrations of Ca2+, but whether such activation is direct is not known [9]. However, currents generated by bestrophin over-expression do not resemble native CaCC currents. The evidence for and against bestrophin proteins forming CaCC is critically reviewed by Duran et al. [5]. Recently, a new gene family, TMEM16 (anoctamin) consisting of 10 members (TMEM16A-K; anoctamin 1-10) has been identified and there is firm evidence that some of these members form chloride channels [4,10]. TMEM16A (anoctamin 1; Ano 1) produces Ca2+-activated Cl- currents with kinetics similar to native CaCC currents recorded from different cell types [2,18-19,21]. Knockdown of TMEM16A greatly reduces currents mediated by calcium-activated chloride channels in submandibular gland cells [21] and smooth muscle cells from pulmonary artery [13]. In TMEM16A(-/-) mice secretion of Ca2+-dependent Cl- secretion by several epithelia is reduced [15,18]. Alternative splicing regulates the voltage- and Ca2+- dependence of TMEM16A and such processing may be tissue-specific manner and thus contribute to functional diversity [6]. There are also reports that TMEM16B (anoctamin 2; Ano 2) supports CaCC activity (e.g.[17]) and in TMEM16B(-/-) mice Ca-activated Cl- currents in the main olfactory epithelium (MOE) and in the vomeronasal organ are virtually absent [1].

Channels and Subunits

CaCC C Show summary »

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How to cite this family page

Database page citation:

Calcium activated chloride channel. Accessed on 29/03/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=130.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Other ion channels. Br J Pharmacol. 172: 5942-5955.