TY - JOUR
T1 - Neocortical potassium currents are enhanced by the antiepileptic drug lamotrigine
AU - Zona, Cristina
AU - Tancredi, Virginia
AU - Longone, Patrizia
AU - D'Arcangelo, Giovanna
AU - D'Antuono, Margherita
AU - Manfredi, Mario
AU - Avoli, Massimo
PY - 2002
Y1 - 2002
N2 - 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 μM) reduced and/or abolished epileptiform discharges induced by 4-aminopyridine (4AP, 100 μM; 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 μM; n = 13) increased a transient, 4AP-sensitive, outward current elicited by depolarizing commands in medium containing voltagegated 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.
AB - 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 μM) reduced and/or abolished epileptiform discharges induced by 4-aminopyridine (4AP, 100 μM; 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 μM; n = 13) increased a transient, 4AP-sensitive, outward current elicited by depolarizing commands in medium containing voltagegated 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.
KW - 4-Aminopyridine
KW - Cortical cells
KW - Epileptiform discharges
KW - K currents
KW - Lamotrigine
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U2 - 10.1046/j.1528-1157.2002.51401.x
DO - 10.1046/j.1528-1157.2002.51401.x
M3 - Article
C2 - 12102669
AN - SCOPUS:0036064909
VL - 43
SP - 685
EP - 690
JO - Epilepsia
JF - Epilepsia
SN - 0013-9580
IS - 7
ER -