title: Epileptiform activity induced by pharmacologic reduction of M-current in the developing hippocampus in vitro.
abstract: OBJECTIVE
  Benign familial neonatal convulsions (BFNCs), an inheritable epilepsy that occurs in neonates but not in adults, is caused by hypofunctional mutations in genes codifying for the M-type K+ current. In an attempt to develop an in vitro model of this disease, we tested whether blocking M-current with linopirdine induces epileptiform activity in brain slices from animals of different ages.
  
  
  METHODS
  Horizontal hippocampus-entorhinal cortex slices were obtained from neonatal (1-2 weeks after birth) and adult (8-9 weeks after birth) rats. Extracellular field recordings of the CA1 region were performed. After recording control conditions, linopirdine was added to the bath, and field activity was recorded continuously for 3 h. 4-Aminopyridine, a drug commonly used to induce epileptiform activity in vitro, was used as a control for our experimental conditions.
  
  
  RESULTS
  Bath perfusion of linopirdine induced epileptiform activity only in slices from neonatal rats. Epileptiform activity consisted of interictal-like and ictal-like activity. In slices from adult rats, linopirdine induced erratic interictal-like activity. In contrast, 4-aminopyridine was able to induce epileptiform activity in slices from both neonatal and adult rats.
  
  
  CONCLUSIONS
  We demonstrated that blockade of M-current in vitro produces epileptiform activity with a developmental pattern similar to that observed in BNFCs. This could be an in vitro model that can be used to study the cellular mechanisms of epileptogenesis and the developmental features of BFNCs, as well as to develop some therapeutic strategies.
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, México City, México. jfpena@cinvestav.mx
authors.forename: Fernando
authors.initials: F
authors.lastname: Peña
authors.forename: Noé
authors.initials: N
authors.lastname: Alavez-Pérez
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D004569:Electroencephalography / Q000187:drug effects / Q000706:statistics & numerical data; D004594:Electrophysiology; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007211:Indoles; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011725:Pyridines; D015761:4-Aminopyridine; C061017:linopirdine