Figure 1.

HCND is required for the function of HCN2 channels. A, ribbon representation of the cryo-EM structure of HCN1 (PDB code 5U6P; Ref. 17). Only two diagonal subunits are shown for clarity. The transmembrane segments (TM) are gray, the HCND is orange, the C-linker is red, the CNBD is blue, and the distal C terminus is green. cAMP is shown in yellow. B, amino acid sequence alignment of the HCND for all four mammalian HCN channel isoforms. Identical residues are shown on a yellow background, conserved residues are on a blue background, and similar residues are on a green background. Letters without a background indicate nonsimilar residues. C and D, representative currents recorded from the WT (C) and ΔHCND mutant (D) mHCN2 channels.