Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) Channels in Epilepsy

Epilepsy is a common brain disorder characterized by the occurrence of spontaneous seizures. These bursts of synchronous firing arise from abnormalities of neuronal networks. Excitability of individual neurons and neuronal networks is largely governed by ion channels and, indeed, abnormalities of a number of ion channels resulting from mutations or aberrant expression and trafficking underlie several types of epilepsy. Here, we focus on the hyperpolarization-activated cyclic nucleotide-gated ion (HCN) channels that conduct I-h current. This conductance plays complex and diverse roles in the regulation of neuronal and network excitability. We describe the normal function of HCN channels and discuss how aberrant expression, assembly, trafficking, and posttranslational modifications contribute to experimental and human epilepsy.