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Dynamic modulation of ANO1/TMEM16A HCO3− permeability by Ca2+/calmodulin

 Jinsei Jung  ;  Joo Hyun Nam  ;  Hyun Woo Park  ;  Uhtaek Oh  ;  Joo-Heon Yoon  ;  Min Goo Lee 
 Proceedings of the National Academy of Sciences of the United States of America, Vol.110(1) : 360-365, 2013 
Journal Title
 Proceedings of the National Academy of Sciences of the United States of America 
Issue Date
Anoctamin 1 (ANO1)/transmembrane protein 16A (TMEM16A) is a calcium-activated anion channel that may play a role in HCO3− secretion in epithelial cells. Here, we report that the anion selectivity of ANO1 is dynamically regulated by the Ca2+/calmodulin complex. Whole-cell current measurements in HEK 293T cells indicated that ANO1 becomes highly permeable to HCO3− at high [Ca2+]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 [Ca2+]i is responsible for changes in anion permeability. Calmodulin physically interacted with ANO1 in a [Ca2+]i-dependent manner, and addition of recombinant calmodulin to the cytosolic side of excised patches reversibly increased PHCO3/PCl. In addition, the high [Ca2+]i-induced increase in HCO3− permeability was reproduced in mouse submandibular gland acinar cells, in which ANO1 plays a critical role in fluid secretion. These results indicate that the HCO3− permeability of ANO1 can be dynamically modulated and that ANO1 may play an important role in cellular HCO3− transport, especially in transepithelial HCO3− secretion.
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1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Yoon, Joo Heon(윤주헌)
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
Jung, Jinsei(정진세) ORCID logo https://orcid.org/0000-0003-1906-6969
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