Neuronal HCN channel function and plasticity

The hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channel is a voltage-gated cation channel that is activated with hyperpolarization. Four subunits, HCN1–4, have thus far been identified. All four subunits are expressed in the central nervous system (CNS), though their expression pattern varies considerably. In many CNS neurons, HCN channels are localised to somato-dendritic compartments where they regulate the resting membrane potential and membrane resistance, and thereby affect synaptic potential shapes and integration and neuronal firing patterns. Emerging evidence suggests that HCN channels are also present within certain axons and synaptic terminals. Modulation of presynaptic HCN channel activity leads to altered synaptic release in a synapse-specific manner. Given that HCN channel function can be modified by activity-dependent and neurotransmitter receptor activation, HCN channels may diversely affect neuronal and network excitability, thereby affecting physiological states such as learning and memory as well as pathophysiological conditions such as epilepsy and depression.