HCN channels pass both Na+ and K+ with relative permeability ratio of ~0.15 to 0.25. The primary sequence of HCN pore region is clearly related to that of highly selective K+ channels. In contrast to nonselective CNG or Na+-channels, both K+ and HCN channels contain a GYG motif in the pore. By affecting the spatial coordination of the GYG sequence in the tetrameric channel complex, other channel domains could control the structural rigidity of the pore and thereby determine whether only K+ or also other monovalent are allowed to permeate.