A structural, functional, and computational analysis suggests pore flexibility as the base for the poor selectivity of CNG channels

Cyclic nucleotide-gated (CNG) channels underlie sensory transduction in photoreceptors and olfactory epithelium and share a high degree of homology with K+ channels. However, these channels conduct Na+ and K+ differently: although K+ channels discriminate with high accuracy Na+ from K+, CNG channels do not discriminate among different cations. By combining electrophysiology, molecular dynamics simulations, and X-ray crystallography we found that the pore region exhibits a dynamic structure. We show that (i) the selectivity filter can adapt to large and small ions with a different geometry and (ii) the pore diameter critically depends on the ion within. We conclude that the pore of CNG channels is highly flexible and that this flexibility is at the basis of their poor ionic selectivity.