HCN1 is a member of a family of pacemaker channels activated by hyperpolarization and regulated by cyclic nucleotides. HCN1 and HCN2 proteins play an important role for motor learning and synapse formation through integration of cerebellar Purkinje cells. The two proteins also shape autonomous activity of single neurons and the periodicity of network oscillations. HCN1 expression is particularly high in the cerebral cortex, hippocampus, cerebellum, and facial motor nucleus. Hyperpolarization of activated cation channels of the HCN gene family such as HCN1, contributes to spontaneous rhythmic activity in both heart and brain. HCN channels pass both Na+ and K+ with relative permeability ratio of ~0.15 to 0.25. The primary sequence of HCN pore region is clearly related to that of highly selective K+ channels. In contrast to nonselective CNG or Na+-channels, both K+ and HCN channels contain a GYG motif in the pore.