Inhibition of muscle acetylcholine receptor by the antiepileptic drug lamotrigine

SOFIA VALLES,; GARBUS INGRID,; BARRANTES FRANCISCO,

Bariloche

Congreso; Argentine Society for Biochemistry and Molecular Biology XXXIX Annual Meeting (SAIB) and Biophysical Society of Argentina XXXII Annual Meeting,; 2003

Argentine Society for Biochemistry and Molecular Biology XXXIX Annual Meeting (SAIB) and Biophysical Society of Argentina XXXII

Some forms of autosomal dominant nocturnal frontal lobe epilepsy(ADNFLE) have been found to be associated with genes codingfor the α4β2 neuronal acetylcholine receptor (AChR). Lamotrigine(LTG) is a triazine compound chemically unrelated to otherantiepileptic drugs. Its major mechanism of action is blocking thevoltage-dependent sodium-channel conductance. Here wecharacterized the effect of LTG on the muscle AChR heterologouslyexpressed in CHOK1/A5 cells by recording the single-channelactivity of the receptor using the patch-clamp technique. LTG wasfound to alter AChR channel kinetics. Exposure to the drug 1)diminished the channel amplitude; 2) caused shortening of thechannel open state; 3) increased burst duration, 4) increased theduration and area of the briefest component of the channel closedstate. In the concentration range tested (50-150 μM), the effectsdid not depend on the dose. We propose that LTG blocks the AChRallowing it to reopen quickly, through a mechanism that iscompatible with that of open channel blockers.