The Ca 2+-activated Cl - channels (CaCCs) are involved in a variety of physiological functions, such as transepithelial anion transport, smooth muscle contraction and olfaction. Recently, the question of the molecular identity of CaCCs has apparently been resolved with the identification of TMEM16A protein (also known as anoctamin-1). Expression of TMEM16A is associated with the appearance of Ca 2+- and voltage-dependent Cl - currents with properties similar to those of native CaCCs. The putative structure of TMEM16A consists of eight transmembrane domains, with both the amino- and the carboxy-terminus protruding in the cytosol. TMEM16A is also characterized by the existence of different protein variants generated by alternative splicing. A close paralogue of TMEM16A, TMEM16B (anoctamin-2), is also associated with CaCC activity, although with different properties. The TMEM16B-dependent channels require higher intracellular Ca 2+ concentrations and have faster activation and deactivation kinetics. Expression of other anoctamins is devoid of detectable channel activity. These proteins, such as TMEM16F (anoctamin-6), may have different functions.
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