Deletion of the potassium channel Kv12.2 causes hippocampal hyperexcitability and epilepsy

Nat Neurosci. 2010 Sep;13(9):1056-8. doi: 10.1038/nn.2610. Epub 2010 Aug 1.

Abstract

We found the voltage-gated K+ channel Kv12.2 to be a potent regulator of excitability in hippocampal pyramidal neurons. Genetic deletion and pharmacologic block of Kv12.2 substantially reduced the firing threshold of these neurons. Kv12.2-/- (also known as Kcnh3-/-) mice showed signs of persistent neuronal hyperexcitability including frequent interictal spiking, spontaneous seizures and increased sensitivity to the chemoconvulsant pentylenetetrazol.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Cell Line
  • Cells, Cultured
  • Convulsants / toxicity
  • Epilepsy / chemically induced
  • Epilepsy / genetics
  • Epilepsy / physiopathology*
  • Ether-A-Go-Go Potassium Channels / antagonists & inhibitors
  • Ether-A-Go-Go Potassium Channels / genetics
  • Ether-A-Go-Go Potassium Channels / metabolism*
  • Female
  • Hippocampus / drug effects
  • Hippocampus / physiopathology*
  • Humans
  • In Vitro Techniques
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / drug effects
  • Neurons / physiology*
  • Pentylenetetrazole / toxicity
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiopathology
  • Seizures / chemically induced
  • Seizures / genetics
  • Seizures / physiopathology
  • Video Recording
  • Xenopus

Substances

  • Convulsants
  • Ether-A-Go-Go Potassium Channels
  • Kcnh3 protein, mouse
  • Pentylenetetrazole