Pore dilatation increases the bicarbonate permeability of CFTR, ANO1 and glycine receptor anion channels.
Authors
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
Citation
JOURNAL OF PHYSIOLOGY-LONDON, Vol.594(11) : 2929-2955, 2016
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.