Lamotrigine protects CHOK1/A5 cells against cell death induced by serum deprivation and Lithium

SOFIA VALLES,; INGRID GARBUS; BARRANTES FRANCISCO,

Pinamar

Congreso; Annual Meeting SAIB, SAB and Protein Symposium; 2005

The nicotinic acetylcholine receptor (AChR) is a membrane proteinpresent in the postsynaptic regions of muscle cells and pre-, periandpostsynaptic regions in nervous cells. Lamotrigine (LTG) blocksin a dose-dependent way the muscle AChR channel in CHO-K1/A5 cells through a mechanism that is compatible with that of openchannel blockers. We evaluated if the blockage seen with LTG onthe muscle AChR affected cell viability, as it was previously seenwith Carbamazepine, another antiepileptic drug that also acts as anopen channel blocker. We studied the neuroprotective action oflithium (Li) and LTG in cultured CHO-K1/A5 cells. Li is bestknown for its neuroprotective action against various insults. In theconcentrations tested (50-200 μM) LTG did not modify cell viabilityas judged by the MTT assay. We then induced cell death by removingserum from the culture for 24 h. Cell survival was reducedsignificantly (25%). Co-incubation with 50 μM LTG protectedcells from death against serum deprivation. However 10 mM Li didnot prevent cell death. Furthermore, 10 mM Li enhanced cell deathby 40% in the absence of serum. We established a TD50 = 25 mMfor Li in the presence of serum in the medium. Thus, the antiepilepticdrug LTG has a robust protective effect on CHO-K1/A5 cell deathinduced by serum deprivation and Li in the culture medium. Thesedata provide new avenues to study the cellular and molecularmechanisms of anticonvulsive drug action.