Hyperpolarization-activated cation currents (Ih) appear in the heart and the brain having crucial role in controlling electrical pacemaker activity, contributing to biological processes such as heartbeat, sleep-wake cycle and synaptic plasticity.The Ih currents are generated by the Hyperpolarization-activated cyclic nucleotide-gated channel family (HCN), which comprises of four homologous members, named HCN1-4. Each HCN subunit consist of six transmembrane domains (TM), a pore region between TM5-TM6 and a binding domain to cyclic nucleotides (CNBD) in the cytoplasmic C-terminus.The HCN subunits can form functionally homomers and can also co-assemble into functionally heteromers
