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Pore dilatation increases the bicarbonate permeability of CFTR, ANO1 and glycine receptor anion channels.

 Ikhyun Jun  ;  Mary Hongying Cheng  ;  Eunji Sim  ;  Jinsei Jung  ;  Bong Lim Suh  ;  Yonjung Kim  ;  Hankil Son  ;  Kyungsoo Park  ;  Chul Hoon Kim  ;  Joo-Heon Yoon  ;  David C. Whitcomb  ;  Ivet Bahar  ;  Min Goo Lee 
 JOURNAL OF PHYSIOLOGY-LONDON, Vol.594(11) : 2929-2955, 2016 
Journal Title
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Anoctamin-1 ; Bicarbonates/metabolism* ; Chloride Channels/chemistry ; Chloride Channels/metabolism* ; Cystic Fibrosis Transmembrane Conductance Regulator/chemistry ; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism* ; HEK293 Cells ; Humans ; Neoplasm Proteins/chemistry ; Neoplasm Proteins/metabolism* ; Nuclear Pore/metabolism* ; Permeability ; Protein Structure, Tertiary ; Receptors, Glycine/chemistry ; Receptors, Glycine/metabolism*
Chloride (Cl(-) ) and bicarbonate (HCO3 (-) ) are two major anions and their permeation through anion channels plays essential roles in our body. However, the mechanism of ion selection by the anion channels is largely unknown. Here, we provide evidence that pore dilatation increases the bicarbonate permeability (P HC O3/ Cl ) of anion channels by reducing energy barriers of size-exclusion and ion dehydration of HCO3 (-) permeation. Molecular, physiological and computational analyses of major anion channels, such as cystic fibrosis transmembrane conductance regulator (CFTR), anoctamin-1(ANO1/TMEM16A) and the glycine receptor (GlyR), revealed that the ion selectivity of anion channels is basically determined by the electric permittivity and diameter of the pore. Importantly, cellular stimuli dynamically modulate the anion selectivity of CFTR and ANO1 by changing the pore size. In addition, pore dilatation by a mutation in the pore-lining region alters the anion selectivity of GlyR. Changes in pore size affected not only the energy barriers of size exclusion but that of ion dehydration by altering the electric permittivity of water-filled cavity in the pore. The dynamic increase in P HC O3/ Cl by pore dilatation may have many physiological and pathophysiological implications ranging from epithelial HCO3 (-) secretion to neuronal excitation.
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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
Kim, Yon Jung(김연정) ORCID logo https://orcid.org/0000-0003-0251-8711
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Park, Kyungsoo(박경수) ORCID logo https://orcid.org/0000-0002-6972-1143
Son, Han kil(손한길)
Yoon, Joo Heon(윤주헌)
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
Jun, Ik Hyun(전익현) ORCID logo https://orcid.org/0000-0002-2160-1679
Jung, Jinsei(정진세) ORCID logo https://orcid.org/0000-0003-1906-6969
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