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Calcium activated chloride channel (CaCC) 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).


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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 [10]. The molecular nature of CaCC has been uncertain with both CLCA, TWEETY and BEST genes having been considered as likely candidates [7,11,14]. 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 [18]. 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 [11] and form chloride channels that are activated by physiological concentrations of Ca2+, but whether such activation is direct is not known [11]. 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. [7]. 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 [6,12]. TMEM16A (anoctamin 1; Ano 1) produces Ca2+-activated Cl- currents with kinetics similar to native CaCC currents recorded from different cell types [2,21-22,27]. Knockdown of TMEM16A greatly reduces currents mediated by calcium-activated chloride channels in submandibular gland cells [27] and smooth muscle cells from pulmonary artery [15]. In TMEM16A(-/-) mice secretion of Ca2+-dependent Cl- secretion by several epithelia is reduced [17,21]. Alternative splicing regulates the voltage- and Ca2+- dependence of TMEM16A and such processing may be tissue-specific manner and thus contribute to functional diversity [8]. There are also reports that TMEM16B (anoctamin 2; Ano 2) supports CaCC activity (e.g.[19]) 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

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How to cite this family page

Database page citation:

Calcium activated chloride channel (CaCC). Accessed on 24/07/2024. IUPHAR/BPS Guide to PHARMACOLOGY,

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Mathie AA, Peters JA, Veale EL, Striessnig J, Kelly E, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Ion channels. Br J Pharmacol. 180 Suppl 2:S145-S222.