[Term] id: PR:000000676 name: potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel protein def: "A cyclic nucleotide-regulated channel protein that has amino- and carboxyl-terminal intracellular domains separated by a domain (common with other ion channels) containing six transmembrane helices (S1-S6) in which the last two helices (S5 and S6) flank a loop, called the pore loop, which determines ion selectivity. The N terminus has a conserved domain that is also present in other voltage-gated potassium and sodium channels. The carboxyl-terminal region contains the cyclic nucleotide-binding domain (CNBD). In addition, there is a structural element called the C-linker, the region connecting the CNBD to the S6 segment, which couples conformational changes in the ligand-binding domain to channel activation. Subunits combine to form the HCN channels. In common with CNG channels, HCN are cation channels that are modulated by cyclic nucleotide binding. Unlike CNG channels, HCN channels are voltage-gated, and are weakly selective for potassium. In contrast to most other voltage-gated channels, HCN channels open upon hyperpolarization and close at positive potential. HCN channels act as a pacemaker by regulating neuronal and cardiac firing rate, but also function as a regulator of membrane resting potential and resistance." [PMID:16382102] comment: Category=family. synonym: "HCN" RELATED [] synonym: "f-channel" EXACT [] xref: PIRSF:PIRSF038514 is_a: PR:000044648 ! cyclic nucleotide-regulated channel protein