Anoctamin-1 | ANO-1 | TMEM -16A
Calcium-dependent chloride channels (Ca-CIC or CaCC family)
CaCCs that are known to occur in humans are encoded by the following genes:
Accessories: CLCA1 - CLCA4
Anoctamins: ANO-1 and ANO-2
Bestrophins: BEST1 - BEST4
CaCC channels are a heterogeneous group of ligand-gated ion channels for chloride that have been identified in many epithelial and endothelial cell types as well as in smooth muscle cells, including proteins from several structurally different families: chloride channel accessory (CLCA), bestrophin (BEST), and calcium-dependent chloride channel anoctamin (ANO or TMEM16) channels. Members of the Ca-CIC family exhibit 7 to 10 transmembrane segments.
Background Information ANO-1
Anoctamin-1 (ANO1), also known as Transmembrane member 16A (TMEM16A), functions as a calcium-activated chloride channel. Ca2+, Sr2+, and Ba2+ activate the channel in smooth muscle and epithelial cells. ATP and calmodulin are essential for its activation. Channel activity is inhibited by CFTR protein and by chloride inhibitors such as niflumic acid (NFA) and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). ANO1 is essential for chloride secretion from epithelial tissues, and has been shown to be a specific marker for cells of Cajal, the pacemaker cells that control smooth muscle contraction. Anoctamin 1 knockout mice exhibit an altered gastric smooth muscle rhythmic contraction. Research studies have identified Anoctamin 1 as a heat sensor in nociceptive neurons. Heat above 44ºC triggers anoctamin 1-dependent depolarization, contributing to the mediation of thermal nociception.
ANO-1 is found in smooth muscle and epithelial cells. It is broadly expressed with higher levels in liver, skeletal muscle and gastrointestinal muscles, especially in human interstitial cells of Cajal (ICC) throughout the gastrointestinal tract. Furthermore, Ano-1 is found in nociceptice neurons.
Transepithelial anion transport and smooth muscle contraction. Required for the normal functioning of the interstitial cells of Cajal (ICCs) which generate electrical pacemaker activity in gastrointestinal smooth muscles. Acts as a major contributor to basal and stimulated chloride conductance in airway epithelial cells and plays an important role in tracheal cartilage development.
Frontal Sinus Squamous Cell Carcinoma, Liver Leiomyoma, multiple myeloma, breast carcinoma, oral cancer, gastrointestinal stromal tumor, frontal sinus cancer
Ezrin, radixin, moesin, RhoA, VAMP3, syntaxins 2 and -4, and syntaxin-binding proteins munc18b and munc18c
Niflumic acid (NFA), carbachol, crofelemer, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), tannic acid, fluoxetine, flufenamic acid, talniflumate
Patch Clamp: whole cell, intracellular solution exchange, temperature control
Reviews and Links
- Huang et al.: International Union of Basic and Clinical Pharmacology. LXXXV: calcium-activated chloride channels(2012) . Pharmacol Rev 64(1):1-15
Transporter classification database:
- 1.A.17.1.1 The plasma membrane Ca2 -activated chloride (IClCa) channel, TMEM16A (Anoctamin 1a; ANO1a)