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

Neuropharmacology. 2013 Jun;69:75-81. doi: 10.1016/j.neuropharm.2012.03.005. Epub 2012 Mar 15.

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'.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anticonvulsants / therapeutic use*
  • Biophysics
  • Cyclic Nucleotide-Gated Cation Channels / drug effects*
  • Cyclic Nucleotide-Gated Cation Channels / genetics
  • Epilepsy / drug therapy*
  • Humans
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • KCNQ Potassium Channels / drug effects*
  • KCNQ Potassium Channels / genetics
  • Mutation / genetics
  • Mutation / physiology
  • Potassium Channels / drug effects*
  • Potassium Channels / genetics
  • Seizures / drug therapy
  • Seizures / physiopathology
  • Subcellular Fractions / drug effects

Substances

  • Anticonvulsants
  • Cyclic Nucleotide-Gated Cation Channels
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • KCNQ Potassium Channels
  • Potassium Channels