Seizing Control of KCC2: A New Therapeutic Target for Epilepsy

Trends Neurosci. 2017 Sep;40(9):555-571. doi: 10.1016/j.tins.2017.06.008. Epub 2017 Aug 10.

Abstract

Deficits in GABAergic inhibition result in the abnormal neuronal activation and synchronization that underlies seizures. However, the molecular mechanisms responsible for transforming a normal brain into an epileptic one remain largely unknown. Hyperpolarizing inhibition mediated by type A GABA (GABAA) receptors is dependent on chloride extrusion by the neuron-specific type 2K+-Cl- cotransporter (KCC2). Loss-of-function mutations in KCC2 are a known cause of infantile epilepsy in humans and KCC2 dysfunction is present in patients with both idiopathic and acquired epilepsy. Here we discuss the growing evidence that KCC2 dysfunction has a central role in the development and severity of the epilepsies.

Keywords: GABA; KCC2; chloride; epilepsy; phosphorylation; seizures.

Publication types

  • Review

MeSH terms

  • Animals
  • Epilepsy / genetics
  • Epilepsy / metabolism*
  • Humans
  • Symporters / genetics
  • Symporters / metabolism*

Substances

  • Symporters
  • potassium-chloride symporters