HCN2 and epilepsy: • Tanshinone has a higher specificity for HCN2 than for the other isoforms. • Fisetin (EC50 approximately 2 μM) is a flavonoid activator of HCN2 channels, which shifts the channel V1/2 toward depolarized potentials. It binds to the CNBD on the channel and shares the same binding pocket as cAMP. • Lamotrigine and Gabapentin increase HCN current amplitude but do not affect channel activation or deactivation kinetics • Gabapentin is used to treat epilepsy and specifically affects the HCN4 isoform with small effect on other HCN isoforms.