Modulation by topiramate of AMPA and kainate mediated calcium influx in cultured cerebral cortical, hippocampal and cerebellar neurons.
The effect of the antiepileptic drug topiramate on Ca2+ uptake through (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionate (AMPA) and kainate (KA) receptors was investigated in different cell culture systems consisting of neurons from the cerebral cortex, hippocampus, and cerebellum. Ca2+ influx was assayed using a fluorescent Ca2+ chelator to monitor changes in the intracellular Ca2+ concentration or cobalt staining to assess the effect of topiramate on Ca2+-permeable AMPA/KA receptors. In all types of neuronal cultures studied, AMPA and KA were found to elicit an influx of Ca2+ in a subset of the neuronal population. Topiramate, at concentrations of 30 and 100 microM, inhibited Ca2+ influx by up to 60%. Modulation of AMPA and KA-evoked Ca2+ influx may contribute to both the antiepileptic and neuroprotective properties of topiramate.
Department of Pharmacology, The Danish University of Pharmaceutical Sciences, Copenhagen, Denmark.
Claus F
CF
Poulsen
Timothy A
TA
Simeone
Thomas E
TE
Maar
Virginia
V
Smith-Swintosky
H Steven
HS
White
Arne
A
Schousboe
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017136:Ion Transport; D007608:Kainic Acid / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D000077236:Topiramate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology*
D000077236:Topiramate; D005632:Fructose; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid; D002118:Calcium