Neocortical potassium currents are enhanced by the antiepileptic drug lamotrigine.
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.
Zona
Cristina
C
Dipartimento di Neuroscienze, Università degli Studi di Roma Tor Vergata, Roma, Italy.
Tancredi
Virginia
V
Longone
Patrizia
P
D'Arcangelo
Giovanna
G
D'Antuono
Margherita
M
Manfredi
Mario
M
Avoli
Massimo
M
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*
D000927:Anticonvulsants; D015221:Potassium Channels; D014227:Triazines; D015761:4-Aminopyridine; D000077213:Lamotrigine