title: HCN and KV7 (M-) channels as targets for epilepsy treatment.
abstract: 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'.
authors.affiliation: Department of Pharmacology, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom. mala.shah@pharmacy.ac.uk
authors.forename: Mala M
authors.initials: MM
authors.lastname: Shah
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Huang
authors.forename: Katiuscia
authors.initials: K
authors.lastname: Martinello
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001703:Biophysics; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000187:drug effects* / Q000235:genetics; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D051656:KCNQ Potassium Channels / Q000187:drug effects* / Q000235:genetics; D009154:Mutation / Q000235:genetics / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects* / Q000235:genetics; D012640:Seizures / Q000188:drug therapy / Q000503:physiopathology; D013347:Subcellular Fractions / Q000187:drug effects
chemical_list: D000927:Anticonvulsants; D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D051656:KCNQ Potassium Channels; D015221:Potassium Channels