1. Enterprise Therapeutics, UK
2. University of Oxford, UK

Abstract

Chloride channels activated by intracellular Ca²⁺ (CaCC) are widely expressed in excitable and non-excitable cells where they perform diverse functions [25]. CaCCs are activated by a rise in intracellular free Ca²⁺ concentration ([Ca²⁺]_i), typically following activation of G_q protein coupled receptors (G_qPCR). This section centres on CaCC channels encoded by the TMEM16A gene (HUGO gene nomenclature: Anoctamin 1). The TMEM16 family consists of 10 paralogs (TMEM16A-K; Anoctamin 1-10). The TMEM16A and TMEM16B genes (ANO1 and ANO2) encode for CaCCs, while the other members function as lipid scramblases or have combined scramblase and non-selective ion channel function [26, 46, 18, 1, 41]. TMEM16A has a broad tissue distribution and a variety of established cellular roles, while the main physiological role for TMEM16B identified thus far is in olfaction [31, 16]. Alternative splicing regulates the voltage- and Ca²⁺-dependence of TMEM16A and such post-transcriptional process may be tissue-specific and contribute to functional diversity [19]. TMEM16A is a potential drug target for a variety of conditions spanning from respiratory to vascular (see "Comments" section for further detail).

Contents

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Database links

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