HCN4 is the main isoform expressed in the sinoatrial node, but low levels of HCN1 and HCN2 have also been reported.
The current through HCN channels, called the pacemaker current (I), plays a key role in the generation and modulation of cardiac rhythmicity, as they are responsible for the spontaneous depolarization in pacemaker action potentials in the heart. HCN4 isoforms are regulated by cCMP and cAMP and these molecules are agonists at I.