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Neocortical Potassium Currents Are Enhanced by the Antiepileptic Drug Lamotrigine
Author(s) -
Zona Cristina,
Tancredi Virginia,
Longone Patrizia,
D'Arcangelo Giovanna,
D'Antuono Margherita,
Manfredi Mario,
Avoli Massimo
Publication year - 2002
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1046/j.1528-1157.2002.51401.x
Subject(s) - 4 aminopyridine , lamotrigine , neocortex , depolarization , neuroscience , tetraethylammonium , electrophysiology , chemistry , anticonvulsant , potassium channel , pharmacology , slice preparation , anesthesia , epilepsy , biophysics , medicine , potassium , biology , organic chemistry
Summary: Purpose: 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 μ M ) reduced and/or abolished epileptiform discharges induced by 4‐aminopyridine (4AP, 100 μ M; n = 10), at doses that were significantly higher than those required to affect epileptiform activity recorded in Mg 2+ ‐free medium (n = 8). We also discovered that in cultured cortical cells, LTG (100–500 μ M; n = 13) increased a transient, 4AP‐sensitive, outward current elicited by depolarizing commands in medium containing voltage‐gated Ca 2+ 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.