title: Neocortical potassium currents are enhanced by the antiepileptic drug lamotrigine.
abstract: OBJECTIVE
  We used field-potential recordings in slices of rat cerebral cortex along with whole-cell patch recordings from rat neocortical cells in culture to test the hypothesis that the antiepileptic drug (AED) lamotrigine (LTG) modulates K+-mediated, hyperpolarizing currents.
  
  
  METHODS
  Extracellular field-potential recordings were performed in neocortical slices obtained from Wistar rats aged 25-50 days. Rat neocortical neurons in culture were subjected to the whole-cell mode of voltage clamping under experimental conditions designed to study voltage-gated K+ currents.
  
  
  RESULTS
  In the in vitro slice preparation, LTG (100-400 microM) reduced and/or abolished epileptiform discharges induced by 4-aminopyridine (4AP, 100 microM; n = 10), at doses that were significantly higher than those required to affect epileptiform activity recorded in Mg2+-free medium (n = 8). We also discovered that in cultured cortical cells, LTG (100-500 microM; n = 13) increased a transient, 4AP-sensitive, outward current elicited by depolarizing commands in medium containing voltage-gated Ca2+ and Na+ channel antagonists. Moreover, we did not observe any change in a late, tetraethylammonium-sensitive outward current.
  
  
  CONCLUSIONS
  Our data indicate that LTG, in addition to the well-known reduction of voltage-gated Na+ currents, potentiates 4AP-sensitive, K+-mediated hyperpolarizing conductances in cortical neurons. This mechanism of action contributes to the anticonvulsant effects exerted by LTG in experimental models of epileptiform discharge, and presumably in clinical practice.
authors.affiliation: Dipartimento di Neuroscienze, Università degli Studi di Roma Tor Vergata, Roma, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Zona
authors.forename: Virginia
authors.initials: V
authors.lastname: Tancredi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Longone
authors.forename: Giovanna
authors.initials: G
authors.lastname: D'Arcangelo
authors.forename: Margherita
authors.initials: M
authors.lastname: D'Antuono
authors.forename: Mario
authors.initials: M
authors.lastname: Manfredi
authors.forename: Massimo
authors.initials: M
authors.lastname: Avoli
mesh_terms: D015761:4-Aminopyridine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D066298:In Vitro Techniques; D000077213:Lamotrigine; D019579:Neocortex / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014227:Triazines / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D015221:Potassium Channels; D014227:Triazines; D015761:4-Aminopyridine; D000077213:Lamotrigine