The HCN subunits can form functional homomers and can also co-assemble into functional heteromers.nThe channels are closely related to each other and share a homology of about 60%. However, their similarity decreases in the cytoplasmic N- and C-termini. The HCN1-4 channels mainly differ from each other in their speed of activation and the extent to which they are modulated by cAMP. HCN1, weakly affected by cAMP, is the fastest channel, followed by HCN2, HCN3 and HCN4.HCN4 is highly expressed in a restricted manner in adult sinoatrial (SA) node, constituting a good molecular marker for the adult cardiac pacemaker and might serve as a unique marker of the developing SA node .mRNA expression of HCN4 is most abundant in medial habenula and anterior and principal relay nuclei of the thalamus.
