Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are protein channels found in the plasma membranes of heart and brain cells that regulate neuronal excitability. HCN is well-known and used for the contribution of its pacemaker function to cardiac rhythm. In addition, several studies have linked the activities of HCN channels to both epilepsy and pain.
A recent study at the Icahn School of Medicine found HCN channels to have substantial potential as a target for major depressive disorder therapeutics. Several animal models of depression have been able to demonstrate that ionic mechanisms play a key role in neuronal homeostasis and dysregulation. Because HCN channels are confirmed to regulate neuronal excitability, they may also have a role in mediating depression-related excitability.
A recent study by Tae, et al using transgenic mice showed that gabapentin impacted several HCN4 channels and had only a slight effect on HCN1 channels. Currently, there are very few drugs known to effect individual HCN channels. Therefore, gabapentin may be useful in studying the function of HCN4 specifically.
Ku SM, Han MH. HCN channel targets for novel antidepressant treatment. Neurotherapeutics. 2017 Jul;14(3):698-715. doi: 10.1007/s13311-017-0538-7.
Tae HS, Smith KM, Phillips AM, et al. Gabapentin modulates HCN4 channel voltage-dependence. Front Pharmacol. 2017 Aug 21;8:554. doi: 10.3389/fphar.2017.00554.