Effects of Levetiracetam on Potassium and Chloride Transport in Cultured Astrocytes and Neuroblastoma Cells
Abstract number :
2.006
Submission category :
Year :
2001
Submission ID :
2851
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
I. Margineanu, PhD, Center for Cell and Molecular Neurobiology, University of Li[egrave]ge, Li[egrave]ge, Belgium; P. Wins, PhD, Center for Cell and Molecular Neurobiology, University of Li[egrave]ge, Li[egrave]ge, Belgium; T. Grisar, MD, PhD, Center for
RATIONALE: The antiepileptic drug levetiracetam (LEV) was reported to inhibit epileptiform neuronal synchronization (Margineanu & Klitgaard, [italic]Pharmacol. Res.[/italic] 42, 281, 2000). Since the mechanisms of the anti-seizure activity of LEV are not fully understood and it was hypothesized that the inhibition of cation-chloride cotransport desynchronizes epileptiform discharges in hippocampal slices without affecting synaptic excitability (Hochman [italic]et al., J. Neurophysiol.[/italic] 81, 45, 1999), we tested the effects of LEV on cation and chloride transport in cultured cells of glial and neuronal origin.
METHODS: We used either primary cultures of astrocytes (isolated from newborn rat cerebral cortex) or the mouse neuroblastoma cell line Neuro-2A (N2A). In astrocytes, Na-K-2Cl cotransport was measured as the bumetamide-sensitive 86Rb+ uptake. In N2A cells, we measured both 86Rb+ and 36Cl- influx. The cellular chloride content was also estimated by chloridometry.
RESULTS: In contrast to furosemide and bumetanide, LEV exerts no direct inhibitory effect on the astrocytic Na-K-2Cl cotransporter. In N2A cells, chloride is mainly transported by a furosemide-sensitive anion exchanger; we also found evidence for a K-Cl cotransport. None of these mechanisms was affected by LEV (10 to 500 [mu]M). The cellular chloride content was also unaffected by LEV. However, a residual influx of 86Rb+, possibly linked to activation of potassium channels, was dose-dependently depressed, up to 60%, by clinically relevant concentrations of LEV, 20 to 100 [mu]M.
CONCLUSIONS: In cultured astrocytes and neuroblastoma cells, no direct, furosemide-like effect of LEV on cation-chloride cotransporters or anion exchangers could be found. It is not excluded, however, that LEV might affect some regulatory mechanisms, notably those controlling the activation of potassium channels.
Support: A grant from UCB SA.
Disclosure: Grant - UCB SA.