Hyperpolarization-activated cation currents (Ih) appear in the heart and the brain and play a crucial role in controlling electrical pacemaker activity, contributing to biological processes such as heartbeat, sleep-wake cycle and synaptic plasticity.nThe Ih currents are generated by the Hyperpolarization-activated Cyclic Nucleotide-gated cannel 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 HCN3 channels are abundant in the brain where high expression of HCN3 mRNA was found in the hypothalamus