title: Kv4.2 knockout mice demonstrate increased susceptibility to convulsant stimulation.
abstract: OBJECTIVE
  Kv4.2 subunits contribute to the pore-forming region of channels that express a transient, A-type K(+) current (A-current) in hippocampal CA1 pyramidal cell dendrites. Here, the A-current plays an important role in signal processing and synaptic integration. Kv4.2 knockout mice show a near elimination of the A-current in area CA1 dendrites, producing increased excitability in this region. In these studies, we evaluated young adult Kv4.2 knockout mice for spontaneous seizures and the response to convulsant stimulation in the whole animal in vivo and in hippocampal slices in vitro.
  
  
  METHODS
  Electroencephalogram electrode-implanted Kv4.2 knockout and wild-type mice were observed for spontaneous behavioral and electrographic seizures. The latency to seizure and status epilepticus onset in Kv4.2 knockout and wild-type mice was assessed following intraperitoneal injection of kainate. Extracellular field potential recordings were performed in hippocampal slices from Kv4.2 knockout and wild-type mice following the bath application of bicuculline.
  
  
  RESULTS
  No spontaneous behavioral or electrographic seizures were observed in Kv4.2 knockout mice. Following kainate, Kv4.2 knockout mice demonstrated a decreased seizure and status epilepticus latency as well as increased mortality compared to wild-type littermates. The background strain modified the seizure susceptibility phenotype in Kv4.2 knockout mice. In response to bicuculline, slices from Kv4.2 knockout mice exhibited an increase in epileptiform bursting in area CA1 as compared to wild-type littermates.
  
  
  CONCLUSIONS
  These studies show that loss of Kv4.2 channels is associated with enhanced susceptibility to convulsant stimulation, supporting the concept that Kv4.2 deficiency may contribute to aberrant network excitability and regulate seizure threshold.
authors.affiliation: Department of Neurology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: L Forbes S
authors.initials: LF
authors.lastname: Barnwell
authors.forename: Joaquin N
authors.initials: JN
authors.lastname: Lugo
authors.forename: Wai L
authors.initials: WL
authors.lastname: Lee
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Willis
authors.forename: Shira J
authors.initials: SJ
authors.lastname: Gertz
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hrachovy
authors.forename: Anne E
authors.initials: AE
authors.lastname: Anderson
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D053447:Channelopathies / Q000503:physiopathology; D003292:Convulsants / Q000494:pharmacology*; D003712:Dendrites / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D004569:Electroencephalography / Q000706:statistics & numerical data; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D012640:Seizures / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology; D051672:Shal Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013226:Status Epilepticus / Q000503:physiopathology
chemical_list: D003292:Convulsants; D051672:Shal Potassium Channels