A distinct site of action at the nicotinic acetylcholine receptor disclosed by the anticonvulsive drug Lamotrigine.

VALLES, A. S.; GARBUS, I.; ANTOLLINI, S. S.; BARRANTES, F. J.

Buzios, Brazil.

Congreso; I Congresso IBRO/LARC de Neurociencias de América Latina, Caribe y Península Ibérica (Neurolatam; 2008

A distinct site of action at the nicotinic acetylcholine receptor disclosed by the anticonvulsive drug Lamotrigine Vallés, A. S., Garbus, I., Antollini, S. S., Barrantes, F. J. Instituto de Investigaciones Bioquímicas de Bahía Blanca-Universidad Nacional del Sur, Bahía Blanca, Argentina Recent studies from our laboratory showed that Lamotrigine (LTG), in the presence of acetylcholine, behaves as a typical muscle nicotinic acetylcholine receptor (AChR) open-channel blocker (Neuroreport. 18: 45, 2007). Objectives: In the present work we studied whether LTG alone had any effect over the AChR. Methods: single-channel and whole-cell  patch-clamp recordings; fluorescence microscopy; ligand binding assays; fluorimetric measurements. Results: LTG was found to activate the AChR. Single-channel patch-clamp recordings showed that the application of LTG (0.05-100 ìM) alone was able to open AChR channels by itself. [125I]a-bungarotoxin binding studies further indicated that LTG does not bind to the canonical ACh binding site. Moreover, fluorescence experiments using the probe crystal violet demonstrated that LTG induces the transition from the resting state to the desensitized state of the AChR in the presence of a-bungarotoxin, that is, when the agonist site is blocked. Allosterically-potentiating ligands or an open-channel blocker exhibited a behavior different from that of LTG. Conclusion: LTG activates the AChR through a site that is different from that of the agonist/competitive antagonists and that of allosterically-potentiating ligands.