AI Article Synopsis
- Lamotrigine (LTG) activates adult muscle nicotinic acetylcholine receptors (AChR) by opening their channels without binding to traditional ACh-binding sites.
- Studies using patch-clamp recordings and [125I]alpha-bungarotoxin-binding reveal that LTG induces a transition of AChR to its desensitized state even when traditional agonist sites are blocked.
- LTG functions through a unique activation mechanism, distinct from full agonists, competitive antagonists, and allosterically-potentiating ligands.
Article Abstract
The anticonvulsive drug Lamotrigine (LTG) is found to activate adult muscle nicotinic acetylcholine receptors (AChR). Single-channel patch-clamp recordings showed that LTG (0.05-400 microM) applied alone is able to open AChR channels. [125I]alpha-bungarotoxin-binding studies further indicate that LTG does not bind to the canonical ACh-binding sites. Fluorescence experiments using the probe crystal violet demonstrate that LTG induces the transition from the resting state to the desensitized state of the AChR in the presence of excess alpha-bungarotoxin, that is, when the agonist site is blocked. Allosterically-potentiating ligands or the open-channel blocker QX-314 exhibited a behavior different from that of LTG. We conclude that LTG activates the AChR through a site that is different from those of full agonists/competitive antagonists and allosterically-potentiating ligands, respectively.
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| http://dx.doi.org/10.1016/j.bbamem.2008.06.012 | DOI Listing |
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