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

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Abstract

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.

Original languageEnglish
Pages (from-to)2929-2955
Number of pages27
JournalJournal of Physiology
Volume594
Issue number11
DOIs
Publication statusPublished - 2016 Jun 1

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All Science Journal Classification (ASJC) codes

  • Physiology

Cite this

Jun, I., Cheng, M. H., Sim, E., Jung, J., Suh, B. L., Kim, Y., Son, H., Park, K., Kim, C. H., Yoon, J. H., Whitcomb, D. C., Bahar, I., & Lee, M. G. (2016). Pore dilatation increases the bicarbonate permeability of CFTR, ANO1 and glycine receptor anion channels. Journal of Physiology, 594(11), 2929-2955. https://doi.org/10.1113/JP271311