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Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):360-5. doi: 10.1073/pnas.1211594110. Epub 2012 Dec 17.

Dynamic modulation of ANO1/TMEM16A HCO3(-) permeability by Ca2+/calmodulin.

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  • 1Department of Pharmacology, Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, Korea.

Erratum in

  • Proc Natl Acad Sci U S A. 2014 Dec 2;111(48):17336.


Anoctamin 1 (ANO1)/transmembrane protein 16A (TMEM16A) is a calcium-activated anion channel that may play a role in HCO(3)(-) secretion in epithelial cells. Here, we report that the anion selectivity of ANO1 is dynamically regulated by the Ca(2+)/calmodulin complex. Whole-cell current measurements in HEK 293T cells indicated that ANO1 becomes highly permeable to HCO(3)(-) at high [Ca(2+)](i). Interestingly, this result was not observed in excised patches, indicating the involvement of cytosolic factors in this process. Further studies revealed that the direct association between ANO1 and calmodulin at high [Ca(2+)](i) is responsible for changes in anion permeability. Calmodulin physically interacted with ANO1 in a [Ca(2+)](i)-dependent manner, and addition of recombinant calmodulin to the cytosolic side of excised patches reversibly increased P(HCO3)/P(Cl). In addition, the high [Ca(2+)](i)-induced increase in HCO(3)(-) permeability was reproduced in mouse submandibular gland acinar cells, in which ANO1 plays a critical role in fluid secretion. These results indicate that the HCO(3)(-) permeability of ANO1 can be dynamically modulated and that ANO1 may play an important role in cellular HCO(3)(-) transport, especially in transepithelial HCO(3)(-) secretion.

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