Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels play an important role in regulating pacemaking activity in the heart and brain. They are regulated by the binding of cyclic nucleotides to a conserved, intracellular cyclic nucleotide-binding domain (CNBD). Binding of cyclic nucleotides increases the rate and extent of activation of the channels and shifts channel activation to less hyperpolarized voltages. In intact channels, cAMP and cGMP are full agonists and cCMP is a partial agonist.
DeBerg, H. A., Islam, S. M., Puljung, M. C., Roux, B., Zagotta, W. N., & Stoll, S. (2015). Allosteric regulation of the cyclic nucleotide-binding domain in HCN channels. Biophysical Journal, 108(2), 192A-193A. https://doi.org/10.1016/j.bpj.2014.11.1064