[Calcium-activated chloride channels: structure, properties, role in physiological and pathological processes].

Ca2+-activated chloride channels (CaCC) are a class of intracellular calcium activated chloride channels that mediate numerous physiological functions. In 2008, the molecular structure of CaCC was determined. CaCC are formed by the protein known as anoctamine 1 (ANO1 or TMEM16A). CaCC mediates the secretion of Cl- in secretory epithelia, such as the airways, salivary glands, intestines, renal tubules, and sweat glands. The presence of CaCC has also been recognized in the vascular muscles, smooth muscles of the respiratory tract, which control vascular tone and hypersensitivity of the respiratory tract. TMEM16A is activated in many cancers; it is believed that TMEM16A is involved in carcinogenesis. TMEM16A is also involved in cancer cells proliferation. The role of TMEM16A in the mechanisms of hypertension, asthma, cystic fibrosis, nociception, and dysfunction of the gastrointestinal tract has been determined. In addition to TMEM16A, its isoforms are involved in other physiological and pathophysiological processes. TMEM16B (or ANO2) is involved in the sense of smell, while ANO6 works like scramblase, and its mutation causes a rare bleeding disorder, known as Scott syndrome. ANO5 is associated with muscle and bone diseases. TMEM16A interacts with various cellular signaling pathways including: epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPK), calmodulin (CaM) kinases, transforming growth factor TGF-β. The review summarizes existing information on known natural and synthetic compounds that can block/modulate CaCC currents and their effect on some pathologies in which CaCC is involved. Ca2+-aktiviruemye khlornye kanaly (CaCC) predstavliaiut soboĭ klass khlornykh kanalov, aktiviruemykh vnutrikletochnym kal'tsiem, kotorye oposreduiut mnogochislennye fiziologicheskie funktsii. V 2008 godu byla opredelena molekuliarnaia struktura CaCC, kotoruiu obrazuet belok anoktamin 1 (ANO1 ili TMEM16A). SaSS oposreduiut sekretsiiu Cl– v sekretornykh épiteliiakh, takikh kak dykhatel'nye puti, sliunnye zhelezy, kishechnik, pochechnye kanal'tsy i potovye zhelezy. Nalichie SaSS ustanovleno takzhe v sosudistykh myshtsakh, gladkikh myshtsakh dykhatel'nykh puteĭ, kotorye kontroliruiut tonus sosudov i giperchuvstvitel'nost' dykhatel'nykh puteĭ. TMEM16A aktiviruetsia pri mnogikh vidakh raka i, takim obrazom, schitaetsia, chto uchastvuet v kantserogeneze. TMEM16A takzhe uchastvuet v proliferatsii rakovykh kletok. Ustanovlena rol' TMEM16A v mekhanizmakh gipertonii, astmy, mukovistsidoza, notsitseptsii, narushenii funktsionirovaniia zheludochno-kishechnogo trakta. V dopolnenie k TMEM16A ustanovleno uchastie ego izoform v drugikh fiziologicheskikh i patofiziologicheskikh protsessakh. Naprimer, TMEM16V (ANO2) uchastvuet v obonianii, togda kak TMEM16F (ANO6) rabotaet kak skramblaza, ego mutatsiia vyzyvaet redkoe narushenie svertyvaemosti krovi - sindrom Skotta; TMEM16E (ANO5) sviazan s zabolevaniiami myshts i kosteĭ. Rassmatrivaetsia vzaimodeĭstvie TMEM16A s razlichnymi kletochnymi signal'nymi putiami: retseptorom épidermal'nogo faktora rosta (EGFR), mitogen-aktivirovannymi proteinkinazami (MAPK), kal'modulin (CaM)-zavisimymi kinazami, transformiruiushchim faktorom rosta TGF-β. V obzore rassmatrivaiutsia prirodnye i sinteticheskie soedineniia, sposobnye blokirovat'/modulirovat' toki SaSS, i ikh vliianie pri nekotorykh vidakh patologii, v kotorykh prinimaiut uchastie SaSS.