Abstract
Various human tissues express the calcium-activated chloride channel Anoctamin 1 (ANO1), also known as TMEM16A. ANO1 allows the passive chloride flux that controls different physiological functions ranging from muscle contraction, fluid and hormone secretion, gastrointestinal motility, and electrical excitability. Overexpression of ANO1 is associated with pathological conditions such as hypertension and cancer. The molecular cloning of ANO1 has led to a surge in structural, functional, and physiological studies of the channel in several tissues. ANO1 is a homodimer channel harboring two pores – one in each monomer – that work independently. Each pore is activated by voltage-dependent binding of two intracellular calcium ions to a high-affinity-binding site. In addition, the binding of phosphatidylinositol 4,5-bisphosphate to sites scattered throughout the cytosolic side of the protein aids the calcium activation process. Furthermore, many pharmacological studies have established ANO1 as a target of promising compounds that could treat several illnesses. This chapter describes our current understanding of the physiological roles of ANO1 and its regulation under physiological conditions as well as new pharmacological compounds with potential therapeutic applications.
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Acknowledgments
The authors thank Dr. José J. De Jesús-Pérez, MSc Ana Elena López, and QFB Carmen Y. Hernández-Carballo for helpful technical assistance and comments.
The Cl− channel research is supported by grant FORDECYT-PRONACES 1308052 2020 from CONACyT, Mexico. Daniel Leon-Aparicio was supported by a Postdoctoral Fellowship # 769266 and 740836 from CONACyT, Mexico. Guadalupe Segura-Covarrubias was supported by a Graduate Student Fellowship # 297721 from CONACyT, Mexico.
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Arreola, J., Pérez-Cornejo, P., Segura-Covarrubias, G., Corral-Fernández, N., León-Aparicio, D., Guzmán-Hernández, M.L. (2022). Function and Regulation of the Calcium-Activated Chloride Channel Anoctamin 1 (TMEM16A). In: Fahlke, C. (eds) Anion Channels and Transporters. Handbook of Experimental Pharmacology, vol 283. Springer, Cham. https://doi.org/10.1007/164_2022_592
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