Invited reviewHCN and KV7 (M-) channels as targets for epilepsy treatment

Voltage-gated ion channels are important determinants of cellular excitability. The Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) and KV7 (M-) channels are voltage-gated ion channels. Both channels are activated at sub-threshold potentials and have biophysical properties that mirror each other. KV7 channels inhibit neuronal excitability. Thus, mutations in KV7 channels that are associated with Benign Familial Neonatal Convulsions (BFNC) are likely to be epileptogenic. Mutations in HCN channels have also been associated with idiopathic epilepsies such as GEFS+. In addition, HCN channel expression and function are modulated during symptomatic epilepsies such as temporal lobe epilepsy. It is, though, unclear as to whether the changes in HCN channel expression and function associated with the various forms of epilepsy promote epileptogenesis or are adaptive. In this review, we discuss this as well as the potential for KV7 and HCN channels as drug targets for the treatment of epilepsy.This article is part of the Special Issue entitled 'New Targets and Approaches to the Treatment of Epilepsy'.

► HCN and KV7/M- channels have biophysical properties that mirror each other. ► Mutations in these channels have been associated with epilepsies. ► The expression and function of these channels is also modulated by seizures. ► We review why modulators of these channels may be beneficial for the treatment of epilepsy.