Anions are essential for keeping cells alive and mediating diverse functions. Chloride (Cl-) and bicarbonate (HCO3-) are two major anions. However we have little information how the anion channel regulates anion permeability. Diverse cellular stimuli can dynamically modulate the bicarbonate permeability (PHCO3/Cl) of anion channels. Activation of WNK1/SPAK kinases can increase the bicarbonate permeability of CFTR, and Ca2+-calmodulin can increase that of anoctamin-1 (ANO1). To figure out the mechanism of anions selection by anion channels, we measured halide ion permeability using patch clamp experiments. And we also measured the permeability of polyatomic anions in same manners. WNK1/SPAK activation altered the permeability of halide ions of CFTR, and increased dielectric constant (ε) and pore size. ANO1 is highly permeable to HCO3- at a high intracellular Ca2+ concentrations ([Ca2+]i > 1uM). The dynamic increase in PHCO3 /PCl of ANO1 was also associated with increases in ε and the diameter of the channel pore. The glycine receptor (GlyR) Cl- channel mediates synaptic inhibition in nervous system. Deletion of proline at the -2 position (P-2’Δ) of the pore-lining second transmembrane segment makes pore size larger. Pore size of wild type (WT) GlyR was 5.3 Å, whereas that of P-2’Δ mutation was 7.1 Å. Also the bicarbonate permeability and dielectric constant of P-2’Δ increased than WT. Here, we provide evidence that pore dilatation increases the bicarbonate permeability of anion channels by reducing energy barriers of size-exclusion and ion dehydration of HCO3 – permeation. Significantly, changing the pore size by cellular stimuli dynamically modulates the anion selectivity of CFTR and ANO1. Additionally, the anion selectivity of GlyR was altered by pore dilation in a mutation in the pore-lining region. The dynamic regulation in PHCO3/Cl by pore size change may have many physiological and pathophysiological implications ranging from epithelial HCO3 – secretion to neuronal excitation.