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Lamotrigine Reduces Voltage‐Gated Sodium Currents in Rat Central Neurons in Culture
Author(s) -
Zona Cristina,
Avoli Massirno
Publication year - 1997
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1157.1997.tb01135.x
Subject(s) - tetrodotoxin , depolarization , sodium channel , chemistry , extracellular , electrophysiology , neuroscience , biophysics , pharmacology , sodium , medicine , biology , biochemistry , organic chemistry
Summary:Purpose : To study the mechanism or mechanisms of action of lamotrigine (LTG) and, in particular, to establish its effects on the function of NA + channels in mammalian central neurons. Methods : Rat cerebellar granule cells in culture were subjected to the whole‐cell mode of voltage clamping under experimental conditions designed to study voltage‐gated Na + currents. Results : Extracellular application of LTG (10–500 μ M , n = 21) decreased in a dose‐related manner a tetrodotoxin‐sensitive inward current that was elicited by depolarizing commands (from −80 to +20mV). The peak amplitude of this Na + ‐mediated current was diminished by 38.8 ± 12.2% (mean ± SD, n = 6) during application of 100 μ M LTG, and the dose‐response curve of this effect indicated an IC 50 145 μM. The reduction in the inward currents produced by LTG was not associate with any signficant change in the current decay, whereas the voltage dependency of the steady‐state inactivation shifted toward more negative values (midpoint of the inactivation curve: –47.5 and –59.0 mV under control conditions and during application of 100 μM LTG, respectively, n = 4). Conclusions : Our findings indicate that LTG reduces the amplitude of voltage‐gated Na + inward current in rat cerebellar granule cells and induces a negative shift of the steady‐state inactivation curve. Both mechanisms may be instrumental in controlling the repetitive firing of action potentials (AP) that occurs in neuronal networks during seizure activity.